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0
DISCUSSION
1
7
[ "b7", "b21", "b7", "b14", "b35", "b36", "b7", "b32" ]
17,164,285
NA|pmid-11250910|pmid-2477553|pmid-12692229|pmid-9649446|pmid-11044073|pmid-15890925|pmid-9649446|pmid-15183342|pmid-9649446|pmid-11044073|pmid-10775614|pmid-9882295|pmid-9649446|pmid-8764039
For example, in one remarkable instance in SIV, poly(A) insertion resulted in a 36 nt PPT (7).
[ "7", "21", "7", "14", "35", "36", "7", "32" ]
94
2,200
1
false
For example, in one remarkable instance in SIV, poly(A) insertion resulted in a 36 nt PPT.
[ "7" ]
For example, in one remarkable instance in SIV, poly(A) insertion resulted in a 36 nt PPT.
true
true
true
true
true
382
0
DISCUSSION
1
7
[ "b7", "b21", "b7", "b14", "b35", "b36", "b7", "b32" ]
17,164,285
NA|pmid-11250910|pmid-2477553|pmid-12692229|pmid-9649446|pmid-11044073|pmid-15890925|pmid-9649446|pmid-15183342|pmid-9649446|pmid-11044073|pmid-10775614|pmid-9882295|pmid-9649446|pmid-8764039
These findings support conclusions derived from the current work, namely, (i) that rU:dA and rA:dT tracts adjacent to and within the PPT, respectively, are to some extent functionally interchangeable (Figure 2a and b, lanes 3) and (ii) that a minimum (+)-strand primer length of 15–17 nt is required for optimal PPT func...
[ "7", "21", "7", "14", "35", "36", "7", "32" ]
325
2,201
0
false
These findings support conclusions derived from the current work, namely, (i) that rU:dA and rA:dT tracts adjacent to and within the PPT, respectively, are to some extent functionally interchangeable (Figure 2a and b, lanes 3) and (ii) that a minimum (+)-strand primer length of 15–17 nt is required for optimal PPT func...
[]
These findings support conclusions derived from the current work, namely, (i) that rU:dA and rA:dT tracts adjacent to and within the PPT, respectively, are to some extent functionally interchangeable (Figure 2a and b, lanes 3) and (ii) that a minimum (+)-strand primer length of 15–17 nt is required for optimal PPT func...
true
true
true
true
true
382
0
DISCUSSION
1
32
[ "b7", "b21", "b7", "b14", "b35", "b36", "b7", "b32" ]
17,164,285
NA|pmid-11250910|pmid-2477553|pmid-12692229|pmid-9649446|pmid-11044073|pmid-15890925|pmid-9649446|pmid-15183342|pmid-9649446|pmid-11044073|pmid-10775614|pmid-9882295|pmid-9649446|pmid-8764039
Finally, it must be noted that our results contrast with a previous biochemical analysis indicating that the rU:dA tract does not play a role in PPT primer selection or initiation of (+) strand DNA synthesis (32).
[ "7", "21", "7", "14", "35", "36", "7", "32" ]
213
2,202
1
false
Finally, it must be noted that our results contrast with a previous biochemical analysis indicating that the rU:dA tract does not play a role in PPT primer selection or initiation of (+) strand DNA synthesis.
[ "32" ]
Finally, it must be noted that our results contrast with a previous biochemical analysis indicating that the rU:dA tract does not play a role in PPT primer selection or initiation of (+) strand DNA synthesis.
true
true
true
true
true
382
0
DISCUSSION
1
7
[ "b7", "b21", "b7", "b14", "b35", "b36", "b7", "b32" ]
17,164,285
NA|pmid-11250910|pmid-2477553|pmid-12692229|pmid-9649446|pmid-11044073|pmid-15890925|pmid-9649446|pmid-15183342|pmid-9649446|pmid-11044073|pmid-10775614|pmid-9882295|pmid-9649446|pmid-8764039
This apparent discrepancy may be due to differences in experimental procedure, most notably, the higher stringency of our assay with respect to enzyme and salt concentration.
[ "7", "21", "7", "14", "35", "36", "7", "32" ]
174
2,203
0
false
This apparent discrepancy may be due to differences in experimental procedure, most notably, the higher stringency of our assay with respect to enzyme and salt concentration.
[]
This apparent discrepancy may be due to differences in experimental procedure, most notably, the higher stringency of our assay with respect to enzyme and salt concentration.
true
true
true
true
true
382
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
The interrupted rA:dT tract constituting the upstream portion of the HIV-1 PPT does not appear to contain determinants for cleavage at the 5′ or 3′ terminus of the (+)-strand primer (Figure 1b and c, lane 6; Figure 2).
[ "7", "2", "37", "38", "29", "32", "39" ]
218
2,204
0
false
The interrupted rA:dT tract constituting the upstream portion of the HIV-1 PPT does not appear to contain determinants for cleavage at the 5′ or 3′ terminus of the (+)-strand primer.
[ "Figure 1b and c, lane 6; Figure 2" ]
The interrupted rA:dT tract constituting the upstream portion of the HIV-1 PPT does not appear to contain determinants for cleavage at the 5′ or 3′ terminus of the (+)-strand primer.
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Instead, the role of this element is to add length to the primer while minimizing internal cleavage (Figure 2).
[ "7", "2", "37", "38", "29", "32", "39" ]
111
2,205
0
false
Instead, the role of this element is to add length to the primer while minimizing internal cleavage.
[ "Figure 2" ]
Instead, the role of this element is to add length to the primer while minimizing internal cleavage.
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Of the three sub-motifs, the rA:dT tract sequence is least conserved among retroviruses, and is essentially absent in bovine leukemia virus and avian myeloblastoma virus (7).
[ "7", "2", "37", "38", "29", "32", "39" ]
174
2,206
1
false
Of the three sub-motifs, the rA:dT tract sequence is least conserved among retroviruses, and is essentially absent in bovine leukemia virus and avian myeloblastoma virus.
[ "7" ]
Of the three sub-motifs, the rA:dT tract sequence is least conserved among retroviruses, and is essentially absent in bovine leukemia virus and avian myeloblastoma virus.
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Furthermore, the length of this element is highly variable, ranging from as few as 4 to as many as 17 nt, and it is usually discontinuous, being interrupted once or twice by one or more Gs or Cs.
[ "7", "2", "37", "38", "29", "32", "39" ]
195
2,207
0
false
Furthermore, the length of this element is highly variable, ranging from as few as 4 to as many as 17 nt, and it is usually discontinuous, being interrupted once or twice by one or more Gs or Cs.
[]
Furthermore, the length of this element is highly variable, ranging from as few as 4 to as many as 17 nt, and it is usually discontinuous, being interrupted once or twice by one or more Gs or Cs.
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Despite this, interrupted rA:dT tracts usually contain a stretch of at least four consecutive rA:dTs, suggesting minor groove narrowing, helical rigidity and other structural features associated with homopolymeric A/T tracts may render the PPT resistant to RNase H. Altered inter-strand base pairing, noted to occur near...
[ "7", "2", "37", "38", "29", "32", "39" ]
433
2,208
0
false
Despite this, interrupted rA:dT tracts usually contain a stretch of at least four consecutive rA:dTs, suggesting minor groove narrowing, helical rigidity and other structural features associated with homopolymeric A/T tracts may render the PPT resistant to RNase H. Altered inter-strand base pairing, noted to occur near...
[ "2,37" ]
Despite this, interrupted rA:dT tracts usually contain a stretch of at least four consecutive rA:dTs, suggesting minor groove narrowing, helical rigidity and other structural features associated with homopolymeric A/T tracts may render the PPT resistant to RNase H. Altered inter-strand base pairing, noted to occur near...
true
true
true
true
true
383
1
DISCUSSION
1
38
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
However, this sub-motif has proven relatively insensitive to mutation in vivo (38) as well as in vitro (29,32), and in the current study, complete disruption of the rA:dT tract via multiple A→G mutations had little effect on (+)-strand initiation (Figure 1b and c, lane 4).
[ "7", "2", "37", "38", "29", "32", "39" ]
273
2,209
1
false
However, this sub-motif has proven relatively insensitive to mutation in vivo as well as in vitro, and in the current study, complete disruption of the rA:dT tract via multiple A→G mutations had little effect on (+)-strand initiation (Figure 1b and c, lane 4).
[ "38", "29,32" ]
However, this sub-motif has proven relatively insensitive to mutation in vivo as well as in vitro, and in the current study, complete disruption of the rA:dT tract via multiple A→G mutations had little effect on (+)-strand initiation (Figure 1b and c, lane 4).
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Amino acid coding requirements may also play a role in determining rA:dT tract composition.
[ "7", "2", "37", "38", "29", "32", "39" ]
91
2,210
0
false
Amino acid coding requirements may also play a role in determining rA:dT tract composition.
[]
Amino acid coding requirements may also play a role in determining rA:dT tract composition.
true
true
true
true
true
383
1
DISCUSSION
1
39
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
The HIV-1 3′ PPT, for example, is embedded within the nef open reading frame, while the central PPT lies within the coding sequence for integrase (39).
[ "7", "2", "37", "38", "29", "32", "39" ]
151
2,211
1
false
The HIV-1 3′ PPT, for example, is embedded within the nef open reading frame, while the central PPT lies within the coding sequence for integrase.
[ "39" ]
The HIV-1 3′ PPT, for example, is embedded within the nef open reading frame, while the central PPT lies within the coding sequence for integrase.
true
true
true
true
true
383
1
DISCUSSION
1
7
[ "b7", "b2", "b37", "b38", "b29", "b32", "b39" ]
17,164,285
pmid-11250910|pmid-12730227|pmid-12972638|pmid-15778225|pmid-16306041|pmid-15004241|pmid-12972638|pmid-15004241|pmid-15778225|pmid-9649446|pmid-11250910|pmid-11875059|pmid-14512562|pmid-7681062|pmid-8764039|pmid-3040055
Finally, accessory proteins, such as NC may alter the sequence requirements of PPT selection/utilization in vivo in a manner not predicted by our simple assays.
[ "7", "2", "37", "38", "29", "32", "39" ]
160
2,212
0
false
Finally, accessory proteins, such as NC may alter the sequence requirements of PPT selection/utilization in vivo in a manner not predicted by our simple assays.
[]
Finally, accessory proteins, such as NC may alter the sequence requirements of PPT selection/utilization in vivo in a manner not predicted by our simple assays.
true
true
true
true
true
383
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
The results of Figure 2 suggest that the optimum length of the plus-strand primer is ∼17 nt, the length of which is roughly equivalent to the distance between the DNA polymerase and RNase H active sites of HIV-1 RT (40,41).
[ "40", "41", "42", "43", "44", "45" ]
223
2,213
0
false
The results of Figure 2 suggest that the optimum length of the plus-strand primer is ∼17 nt, the length of which is roughly equivalent to the distance between the DNA polymerase and RNase H active sites of HIV-1 RT.
[ "40,41" ]
The results of Figure 2 suggest that the optimum length of the plus-strand primer is ∼17 nt, the length of which is roughly equivalent to the distance between the DNA polymerase and RNase H active sites of HIV-1 RT.
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
This suggests that positioning of RT over the hybrid duplex may play an important role in hydrolysis at the PPT-U3 junction.
[ "40", "41", "42", "43", "44", "45" ]
124
2,214
0
false
This suggests that positioning of RT over the hybrid duplex may play an important role in hydrolysis at the PPT-U3 junction.
[]
This suggests that positioning of RT over the hybrid duplex may play an important role in hydrolysis at the PPT-U3 junction.
true
true
true
true
true
384
2
DISCUSSION
1
42
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
Normally, HIV-1 RT binds a hybrid duplex containing two recessed RNA termini such that the polymerase active site is located over the DNA strand opposite the RNA 5′ terminus (42).
[ "40", "41", "42", "43", "44", "45" ]
179
2,215
1
false
Normally, HIV-1 RT binds a hybrid duplex containing two recessed RNA termini such that the polymerase active site is located over the DNA strand opposite the RNA 5′ terminus.
[ "42" ]
Normally, HIV-1 RT binds a hybrid duplex containing two recessed RNA termini such that the polymerase active site is located over the DNA strand opposite the RNA 5′ terminus.
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
In the case of the (+)-strand primer/DNA hybrid, this would place the RNase H domain over the RNA strand near the PPT-U3 junction.
[ "40", "41", "42", "43", "44", "45" ]
130
2,216
0
false
In the case of the (+)-strand primer/DNA hybrid, this would place the RNase H domain over the RNA strand near the PPT-U3 junction.
[]
In the case of the (+)-strand primer/DNA hybrid, this would place the RNase H domain over the RNA strand near the PPT-U3 junction.
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
This preferred mode of binding may explain why G-tract mutations (i.e.
[ "40", "41", "42", "43", "44", "45" ]
70
2,217
0
false
This preferred mode of binding may explain why G-tract mutations (i.e.
[]
This preferred mode of binding may explain why G-tract mutations (i.e.
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
rG→rA) are more likely to result in internal PPT cleavage than the inverse substitutions (rA→rG) within the rA:dT tract, since the RNase H domain of HIV-1 RT (located at or near PPT position −1) would be expected to be in much closer proximity to the former sub-motif.
[ "40", "41", "42", "43", "44", "45" ]
268
2,218
0
false
rG→rA) are more likely to result in internal PPT cleavage than the inverse substitutions (rA→rG) within the rA:dT tract, since the RNase H domain of HIV-1 RT (located at or near PPT position −1) would be expected to be in much closer proximity to the former sub-motif.
[]
rG→rA) are more likely to result in internal PPT cleavage than the inverse substitutions (rA→rG) within the rA:dT tract, since the RNase H domain of HIV-1 RT (located at or near PPT position −1) would be expected to be in much closer proximity to the former sub-motif.
false
true
true
true
false
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
It also appears, however, that in contrast to an RNA/DNA hybrid of random sequence, positioning of RT on a PPT/DNA hybrid is largely independent of the location of the primer 5′ terminus, since (+)-strand initiation is unaffected by the 5′-AAAAG-3′ insertion in substrate PS-9 (Figure 2a and b, lanes W and 2).
[ "40", "41", "42", "43", "44", "45" ]
310
2,219
0
false
It also appears, however, that in contrast to an RNA/DNA hybrid of random sequence, positioning of RT on a PPT/DNA hybrid is largely independent of the location of the primer 5′ terminus, since (+)-strand initiation is unaffected by the 5′-AAAAG-3′ insertion in substrate PS-9 (Figure 2a and b, lanes W and 2).
[]
It also appears, however, that in contrast to an RNA/DNA hybrid of random sequence, positioning of RT on a PPT/DNA hybrid is largely independent of the location of the primer 5′ terminus, since (+)-strand initiation is unaffected by the 5′-AAAAG-3′ insertion in substrate PS-9 (Figure 2a and b, lanes W and 2).
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
This also argues that stepwise digestion of the substrate from the RNA 5′ terminus (43,44) may not be essential for PPT selection.
[ "40", "41", "42", "43", "44", "45" ]
130
2,220
0
false
This also argues that stepwise digestion of the substrate from the RNA 5′ terminus may not be essential for PPT selection.
[ "43,44" ]
This also argues that stepwise digestion of the substrate from the RNA 5′ terminus may not be essential for PPT selection.
true
true
true
true
true
384
2
DISCUSSION
1
40
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
However, it is clear that shortening the primer adversely affects both (+)-strand initiation and primer removal (Figure 2), most likely due to reduced affinity of RT for the smaller hybrid.
[ "40", "41", "42", "43", "44", "45" ]
189
2,221
0
false
However, it is clear that shortening the primer adversely affects both (+)-strand initiation and primer removal (Figure 2), most likely due to reduced affinity of RT for the smaller hybrid.
[]
However, it is clear that shortening the primer adversely affects both (+)-strand initiation and primer removal (Figure 2), most likely due to reduced affinity of RT for the smaller hybrid.
true
true
true
true
true
384
2
DISCUSSION
1
45
[ "b40", "b41", "b42", "b43", "b44", "b45" ]
17,164,285
pmid-9649446|pmid-15183342|pmid-15183342|pmid-15909999|pmid-1913209|pmid-11250910|pmid-1720554|pmid-1374166|pmid-8567660|pmid-11035788|pmid-10956669|pmid-7545436
Dissociation of the hybrid is probably not an important factor, since the Tm of even the shortest primer evaluated (substrate PS-13; Figure 2a and b, lane 6) would be expected to exceed 42°C (45).
[ "40", "41", "42", "43", "44", "45" ]
196
2,222
1
false
Dissociation of the hybrid is probably not an important factor, since the Tm of even the shortest primer evaluated (substrate PS-13; Figure 2a and b, lane 6) would be expected to exceed 42°C.
[ "45" ]
Dissociation of the hybrid is probably not an important factor, since the Tm of even the shortest primer evaluated (substrate PS-13; Figure 2a and b, lane 6) would be expected to exceed 42°C.
true
true
true
true
true
384
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Finally, our results indicate that in HIV-1, determinants for cleavage at, and initiation from the PPT-U3 junction reside within and immediately adjacent to the rG:dC tract, even when this is displaced to other locations within the PPT (Figure 1b, lanes 1 and 2).
[ "34", "2", "20", "37", "31" ]
263
2,223
0
false
Finally, our results indicate that in HIV-1, determinants for cleavage at, and initiation from the PPT-U3 junction reside within and immediately adjacent to the rG:dC tract, even when this is displaced to other locations within the PPT.
[ "Figure 1b, lanes 1 and 2" ]
Finally, our results indicate that in HIV-1, determinants for cleavage at, and initiation from the PPT-U3 junction reside within and immediately adjacent to the rG:dC tract, even when this is displaced to other locations within the PPT.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Furthermore, in agreement with the recent findings of Schultz et al.
[ "34", "2", "20", "37", "31" ]
68
2,224
0
false
Furthermore, in agreement with the recent findings of Schultz et al.
[]
Furthermore, in agreement with the recent findings of Schultz et al.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
(34), −4rG, −2rG and +1rA were found to be of particular significance in defining cleavage specificity.
[ "34", "2", "20", "37", "31" ]
103
2,225
1
false
, −4rG, −2rG and +1rA were found to be of particular significance in defining cleavage specificity.
[ "34" ]
, −4rG, −2rG and +1rA were found to be of particular significance in defining cleavage specificity.
false
false
true
true
false
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Using nucleoside analogs, we were able to modulate the chemical composition of purines at these positions to determine which exocyclic moieties were critical in this regard.
[ "34", "2", "20", "37", "31" ]
173
2,226
0
false
Using nucleoside analogs, we were able to modulate the chemical composition of purines at these positions to determine which exocyclic moieties were critical in this regard.
[]
Using nucleoside analogs, we were able to modulate the chemical composition of purines at these positions to determine which exocyclic moieties were critical in this regard.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
The presence of a 2-NH2 group at position −2 and the absence of this group at position +1, proved essential for directing cleavage at the PPT-U3 junction.
[ "34", "2", "20", "37", "31" ]
154
2,227
0
false
The presence of a 2-NH2 group at position −2 and the absence of this group at position +1, proved essential for directing cleavage at the PPT-U3 junction.
[]
The presence of a 2-NH2 group at position −2 and the absence of this group at position +1, proved essential for directing cleavage at the PPT-U3 junction.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
In the former case, the 2-NH2 group also plays a role in preventing internal cleavage of the PPT at or near position −2.
[ "34", "2", "20", "37", "31" ]
120
2,228
0
false
In the former case, the 2-NH2 group also plays a role in preventing internal cleavage of the PPT at or near position −2.
[]
In the former case, the 2-NH2 group also plays a role in preventing internal cleavage of the PPT at or near position −2.
true
true
true
true
true
385
3
DISCUSSION
1
2
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Intriguingly, only two residues directly contact RNA bases in the vicinity of the RNase H domain in the HIV-1 RT-PPT/DNA co-crystal structure, namely Q475 and R448 of the RNase H primer grip at positions −2 and +1, respectively, relative to the scissile phosphate identified in that structure (2).
[ "34", "2", "20", "37", "31" ]
297
2,229
1
false
Intriguingly, only two residues directly contact RNA bases in the vicinity of the RNase H domain in the HIV-1 RT-PPT/DNA co-crystal structure, namely Q475 and R448 of the RNase H primer grip at positions −2 and +1, respectively, relative to the scissile phosphate identified in that structure.
[ "2" ]
Intriguingly, only two residues directly contact RNA bases in the vicinity of the RNase H domain in the HIV-1 RT-PPT/DNA co-crystal structure, namely Q475 and R448 of the RNase H primer grip at positions −2 and +1, respectively, relative to the scissile phosphate identified in that structure.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Furthermore, contacts occur at or near position 2 of the purines in these locations.
[ "34", "2", "20", "37", "31" ]
84
2,230
0
false
Furthermore, contacts occur at or near position 2 of the purines in these locations.
[]
Furthermore, contacts occur at or near position 2 of the purines in these locations.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
This raises the possibility that steric interference and/or disruption of specific hydrogen bonds at positions −2 and +1 may directly influence whether or not cleavage occurs at the PPT-U3 junction.
[ "34", "2", "20", "37", "31" ]
198
2,231
0
false
This raises the possibility that steric interference and/or disruption of specific hydrogen bonds at positions −2 and +1 may directly influence whether or not cleavage occurs at the PPT-U3 junction.
[]
This raises the possibility that steric interference and/or disruption of specific hydrogen bonds at positions −2 and +1 may directly influence whether or not cleavage occurs at the PPT-U3 junction.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
For example, a +1rA→rG substitution would be expected to create a steric clash with residue R448 of HIV-1 RT by introducing a relatively bulky amino group at position 2 of the the purine.
[ "34", "2", "20", "37", "31" ]
187
2,232
0
false
For example, a +1rA→rG substitution would be expected to create a steric clash with residue R448 of HIV-1 RT by introducing a relatively bulky amino group at position 2 of the the purine.
[]
For example, a +1rA→rG substitution would be expected to create a steric clash with residue R448 of HIV-1 RT by introducing a relatively bulky amino group at position 2 of the the purine.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
In contrast, a −2rA→rI substitution, which would not change the constituent at the purine 2-position, would have no apparent effect.
[ "34", "2", "20", "37", "31" ]
132
2,233
0
false
In contrast, a −2rA→rI substitution, which would not change the constituent at the purine 2-position, would have no apparent effect.
[]
In contrast, a −2rA→rI substitution, which would not change the constituent at the purine 2-position, would have no apparent effect.
true
true
true
true
true
385
3
DISCUSSION
1
34
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
A model depicting such a scenario is shown in Figure 7.
[ "34", "2", "20", "37", "31" ]
55
2,234
0
false
A model depicting such a scenario is shown in Figure 7.
[]
A model depicting such a scenario is shown in Figure 7.
true
true
true
true
true
385
3
DISCUSSION
1
31
[ "b34", "b2", "b20", "b37", "b31" ]
17,164,285
pmid-7681062|pmid-11250910|pmid-11939780|pmid-16306040|pmid-11250910|pmid-15004241|pmid-11875059|pmid-14636594
Alternatively, the importance of −2rG and +1rA may stem from unusual base pairing at these positions (20,37), wherein the 2-NH2-substituted purine may disrupt important cis-acting signals directing RT-binding and cleavage, and/or enhanced helical flexibility noted to occur within 5′-rArGrA-3′ steps (31).
[ "34", "2", "20", "37", "31" ]
305
2,235
1
false
Alternatively, the importance of −2rG and +1rA may stem from unusual base pairing at these positions, wherein the 2-NH2-substituted purine may disrupt important cis-acting signals directing RT-binding and cleavage, and/or enhanced helical flexibility noted to occur within 5′-rArGrA-3′ steps.
[ "20,37", "31" ]
Alternatively, the importance of −2rG and +1rA may stem from unusual base pairing at these positions, wherein the 2-NH2-substituted purine may disrupt important cis-acting signals directing RT-binding and cleavage, and/or enhanced helical flexibility noted to occur within 5′-rArGrA-3′ steps.
true
true
true
true
true
385
4
DISCUSSION
1
2
[ "b2" ]
17,164,285
pmid-11250910
Steric interference upon rA→rG substitution at position +1.
[ "2" ]
59
2,236
0
false
Steric interference upon rA→rG substitution at position +1.
[]
Steric interference upon rA→rG substitution at position +1.
true
true
true
true
true
386
4
DISCUSSION
1
2
[ "b2" ]
17,164,285
pmid-11250910
Panels reflect changes to the RT–nucleic acid interface when A, G or I is present 1 nt 3′ of the scissile phosphate.
[ "2" ]
116
2,237
0
false
Panels reflect changes to the RT–nucleic acid interface when A, G or I is present 1 nt 3′ of the scissile phosphate.
[]
Panels reflect changes to the RT–nucleic acid interface when A, G or I is present 1 nt 3′ of the scissile phosphate.
true
true
true
true
true
386
4
DISCUSSION
1
2
[ "b2" ]
17,164,285
pmid-11250910
R448 of the RNase H primer grip and the base at position +1 are shown in yellow.
[ "2" ]
80
2,238
0
false
R448 of the RNase H primer grip and the base at position +1 are shown in yellow.
[]
R448 of the RNase H primer grip and the base at position +1 are shown in yellow.
true
true
true
true
true
386
4
DISCUSSION
1
2
[ "b2" ]
17,164,285
pmid-11250910
Space-filled atoms include the 2-H and 2-NH2 groups of A/I and G, respectively, as well as side-chain amine hydrogen of R448.
[ "2" ]
125
2,239
0
false
Space-filled atoms include the 2-H and 2-NH2 groups of A/I and G, respectively, as well as side-chain amine hydrogen of R448.
[]
Space-filled atoms include the 2-H and 2-NH2 groups of A/I and G, respectively, as well as side-chain amine hydrogen of R448.
true
true
true
true
true
386
4
DISCUSSION
1
2
[ "b2" ]
17,164,285
pmid-11250910
Models are derived from the HIV-1 RT-PPT/DNA crystal structure (2), and nucleoside variants constructed using DS Viewer (Accelyrs, San Diego, CA).
[ "2" ]
146
2,240
1
false
Models are derived from the HIV-1 RT-PPT/DNA crystal structure, and nucleoside variants constructed using DS Viewer (Accelyrs, San Diego, CA).
[ "2" ]
Models are derived from the HIV-1 RT-PPT/DNA crystal structure, and nucleoside variants constructed using DS Viewer (Accelyrs, San Diego, CA).
true
true
true
true
true
386
5
DISCUSSION
1
46
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
Although there appears to be no single structural feature to explain the effects of each analog substitution at position −4rG (Figure 6), it is clear that a 6-NH2-substituted purine is poorly tolerated at that position, as is the reversal in exocyclic group orientation resulting from rG→riG substitution.
[ "46", "47", "48", "49", "48" ]
305
2,241
0
false
Although there appears to be no single structural feature to explain the effects of each analog substitution at position −4rG (Figure 6), it is clear that a 6-NH2-substituted purine is poorly tolerated at that position, as is the reversal in exocyclic group orientation resulting from rG→riG substitution.
[]
Although there appears to be no single structural feature to explain the effects of each analog substitution at position −4rG, it is clear that a 6-NH2-substituted purine is poorly tolerated at that position, as is the reversal in exocyclic group orientation resulting from rG→riG substitution.
true
true
true
true
true
387
5
DISCUSSION
1
46
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
Since no direct contact between HIV-1 RT and the RNA strand of an RNA–DNA hybrid is predicted to occur at PPT position −4 (relative to the scissile phosphate), local steric interference with RT-binding is an unlikely explanation for our observations.
[ "46", "47", "48", "49", "48" ]
250
2,242
0
false
Since no direct contact between HIV-1 RT and the RNA strand of an RNA–DNA hybrid is predicted to occur at PPT position −4 (relative to the scissile phosphate), local steric interference with RT-binding is an unlikely explanation for our observations.
[]
Since no direct contact between HIV-1 RT and the RNA strand of an RNA–DNA hybrid is predicted to occur at PPT position −4 (relative to the scissile phosphate), local steric interference with RT-binding is an unlikely explanation for our observations.
true
true
true
true
true
387
5
DISCUSSION
1
46
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
However, it is possible that curvature of the helix is affected by substitution of an amino group for the 6-oxygen moiety of −4rG, which could indirectly affect the manner in which the duplex is contacted by HIV-1 RT.
[ "46", "47", "48", "49", "48" ]
217
2,243
0
false
However, it is possible that curvature of the helix is affected by substitution of an amino group for the 6-oxygen moiety of −4rG, which could indirectly affect the manner in which the duplex is contacted by HIV-1 RT.
[]
However, it is possible that curvature of the helix is affected by substitution of an amino group for the 6-oxygen moiety of −4rG, which could indirectly affect the manner in which the duplex is contacted by HIV-1 RT.
true
true
true
true
true
387
5
DISCUSSION
1
48
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
This might manifest itself via electronic effects on base stacking (46,47), altered coordination of solvent cations (48), or perhaps most intriguingly, by direct electronic (or steric) interaction between/among exocyclic groups on adjacent purines.
[ "46", "47", "48", "49", "48" ]
248
2,244
1
false
This might manifest itself via electronic effects on base stacking, altered coordination of solvent cations, or perhaps most intriguingly, by direct electronic (or steric) interaction between/among exocyclic groups on adjacent purines.
[ "46,47", "48" ]
This might manifest itself via electronic effects on base stacking, altered coordination of solvent cations, or perhaps most intriguingly, by direct electronic (or steric) interaction between/among exocyclic groups on adjacent purines.
true
true
true
true
true
387
5
DISCUSSION
1
49
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
For example, within the interrupted A-tract of the HIV-1 PPT the interatomic distances between 6-NH2 nitrogens of adjacent purines are as little as 2.9 Å, suggesting the possibility of direct electronic interaction between bases (49).
[ "46", "47", "48", "49", "48" ]
234
2,245
1
false
For example, within the interrupted A-tract of the HIV-1 PPT the interatomic distances between 6-NH2 nitrogens of adjacent purines are as little as 2.9 Å, suggesting the possibility of direct electronic interaction between bases.
[ "49" ]
For example, within the interrupted A-tract of the HIV-1 PPT the interatomic distances between 6-NH2 nitrogens of adjacent purines are as little as 2.9 Å, suggesting the possibility of direct electronic interaction between bases.
true
true
true
true
true
387
5
DISCUSSION
1
46
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
One could envision, therefore, that inserting an amino group into a string of adjacent 6-oxygen moieties within a G-tract could alter the trajectory of the helix.
[ "46", "47", "48", "49", "48" ]
162
2,246
0
false
One could envision, therefore, that inserting an amino group into a string of adjacent 6-oxygen moieties within a G-tract could alter the trajectory of the helix.
[]
One could envision, therefore, that inserting an amino group into a string of adjacent 6-oxygen moieties within a G-tract could alter the trajectory of the helix.
true
true
true
true
true
387
5
DISCUSSION
1
48
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
This is particularly plausible since elements bonded at the purine 6-position comprise one wall of the helical major groove, which like the minor groove in dA:dT and rA:dT tracts, is compressed in homopolymeric dG:dC stretches (48).
[ "46", "47", "48", "49", "48" ]
232
2,247
1
false
This is particularly plausible since elements bonded at the purine 6-position comprise one wall of the helical major groove, which like the minor groove in dA:dT and rA:dT tracts, is compressed in homopolymeric dG:dC stretches.
[ "48" ]
This is particularly plausible since elements bonded at the purine 6-position comprise one wall of the helical major groove, which like the minor groove in dA:dT and rA:dT tracts, is compressed in homopolymeric dG:dC stretches.
true
true
true
true
true
387
5
DISCUSSION
1
46
[ "b46", "b47", "b48", "b49", "b48" ]
17,164,285
pmid-8554595|pmid-15788750|pmid-12717729|pmid-521211|pmid-12717729
However, since a homopolymeric rG:dC tract has never been resolved by X-ray crystallography or NMR, the spatial relationship between 6-oxygen groups on adjacent purines in this context remains speculative.
[ "46", "47", "48", "49", "48" ]
205
2,248
0
false
However, since a homopolymeric rG:dC tract has never been resolved by X-ray crystallography or NMR, the spatial relationship between 6-oxygen groups on adjacent purines in this context remains speculative.
[]
However, since a homopolymeric rG:dC tract has never been resolved by X-ray crystallography or NMR, the spatial relationship between 6-oxygen groups on adjacent purines in this context remains speculative.
true
true
true
true
true
387
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
The biologically active form of vitamin D, 1α, 25-dihydroxyvitamin D3 (1α,25(OH)2D3)), is required for mineral homeostasis and skeletal integrity, as well as controlling cell growth and differentiation in several tissues (1).
[ "1", "2", "3", "4", "5", "6", "7" ]
225
2,249
1
false
The biologically active form of vitamin D, 1α, 25-dihydroxyvitamin D3 2D3)), is required for mineral homeostasis and skeletal integrity, as well as controlling cell growth and differentiation in several tissues.
[ "1α,25(OH", "1" ]
The biologically active form of vitamin D, 1α, 25-dihydroxyvitamin D3 2D3)), is required for mineral homeostasis and skeletal integrity, as well as controlling cell growth and differentiation in several tissues.
true
true
true
true
true
388
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
In the body, the amount of 1α,25(OH)2D3 is tightly controlled by several enzymes that are transcribed from genes belonging to the cytochrome P450 (CYP) family.
[ "1", "2", "3", "4", "5", "6", "7" ]
159
2,250
0
false
In the body, the amount of 1α,25(OH)2D3 is tightly controlled by several enzymes that are transcribed from genes belonging to the cytochrome P450 (CYP) family.
[]
In the body, the amount of 1α,25(OH)2D3 is tightly controlled by several enzymes that are transcribed from genes belonging to the cytochrome P450 (CYP) family.
true
true
true
true
true
388
0
INTRODUCTION
1
2
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
This gene family encodes a wide variety of enzymes that are needed in the oxidative metabolism of a number of endogenous and exogenous compounds (2).
[ "1", "2", "3", "4", "5", "6", "7" ]
149
2,251
1
false
This gene family encodes a wide variety of enzymes that are needed in the oxidative metabolism of a number of endogenous and exogenous compounds.
[ "2" ]
This gene family encodes a wide variety of enzymes that are needed in the oxidative metabolism of a number of endogenous and exogenous compounds.
true
true
true
true
true
388
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
One of the enzymes needed in the metabolism of 1α,25(OH)2D3 is the protein product of the CYP27B1 gene, 25-hydroxyvitamin D3 (25(OH)D3)
[ "1", "2", "3", "4", "5", "6", "7" ]
135
2,252
0
false
One of the enzymes needed in the metabolism of 1α,25(OH)2D3 is the protein product of the CYP27B1 gene, 25-hydroxyvitamin D3 D3)
[ "25(OH" ]
One of the enzymes needed in the metabolism of 1α,25(OH)2D3 is the protein product of the CYP27B1 gene, 25-hydroxyvitamin D3 D3)
true
true
false
true
false
388
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
1α -hydroxylase.
[ "1", "2", "3", "4", "5", "6", "7" ]
16
2,253
0
false
1α -hydroxylase.
[]
1α -hydroxylase.
false
false
true
true
false
388
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
It has an important role in the synthesis of 1α,25(OH)2D3 because it catalyzes the metabolic activation of the main circulating form of vitamin D, 25(OH)D3, into 1α,25(OH)2D3 (3).
[ "1", "2", "3", "4", "5", "6", "7" ]
179
2,254
1
false
It has an important role in the synthesis of 1α,25(OH)2D3 because it catalyzes the metabolic activation of the main circulating form of vitamin D, 25(OH)D3, into 1α,25(OH)2D3.
[ "3" ]
It has an important role in the synthesis of 1α,25(OH)2D3 because it catalyzes the metabolic activation of the main circulating form of vitamin D, 25(OH)D3, into 1α,25(OH)2D3.
true
true
true
true
true
388
0
INTRODUCTION
1
4
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
CYP27B1 gene expression is negatively regulated by 1α,25(OH)2D3, and this has been proposed to occur via a negative vitamin D response element (nVDRE), located ∼500 bp upstream from transcription start site (TSS) (4).
[ "1", "2", "3", "4", "5", "6", "7" ]
217
2,255
1
false
CYP27B1 gene expression is negatively regulated by 1α,25(OH)2D3, and this has been proposed to occur via a negative vitamin D response element (nVDRE), located ∼500 bp upstream from transcription start site (TSS).
[ "4" ]
CYP27B1 gene expression is negatively regulated by 1α,25(OH)2D3, and this has been proposed to occur via a negative vitamin D response element (nVDRE), located ∼500 bp upstream from transcription start site (TSS).
true
true
true
true
true
388
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
The down-regulation of this gene by 1α,25(OH)2D3 is a cell-type and tissue-restricted phenomenon.
[ "1", "2", "3", "4", "5", "6", "7" ]
97
2,256
0
false
The down-regulation of this gene by 1α,25(OH)2D3 is a cell-type and tissue-restricted phenomenon.
[]
The down-regulation of this gene by 1α,25(OH)2D3 is a cell-type and tissue-restricted phenomenon.
true
true
true
true
true
388
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
In the body, the major expression site of the CYP27B1 gene and its protein product, 25(OH)D3 1α-hydroxylase (CYP27B1), is the kidney.
[ "1", "2", "3", "4", "5", "6", "7" ]
133
2,257
0
false
In the body, the major expression site of the CYP27B1 gene and its protein product, 25(OH)D3 1α-hydroxylase, is the kidney.
[ "CYP27B1" ]
In the body, the major expression site of the CYP27B1 gene and its protein product, 25(OH)D3 1α-hydroxylase, is the kidney.
true
true
true
true
true
388
0
INTRODUCTION
1
5
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
Within this organ, both the mRNA and the protein product have been observed to be repressed in the presence of 1α,25(OH)2D3 in the proximal tubules only (5).
[ "1", "2", "3", "4", "5", "6", "7" ]
157
2,258
1
false
Within this organ, both the mRNA and the protein product have been observed to be repressed in the presence of 1α,25(OH)2D3 in the proximal tubules only.
[ "5" ]
Within this organ, both the mRNA and the protein product have been observed to be repressed in the presence of 1α,25(OH)2D3 in the proximal tubules only.
true
true
true
true
true
388
0
INTRODUCTION
1
6
[ "B1", "B2", "B3", "B4", "B5", "B6", "B7" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
The CYP27B1 gene is also expressed in extra renal sites (6), however the suppression of the gene by 1α,25(OH)2D3 has been described only in a few other cell lines derived from other tissues, such as colon-derived cells (7).
[ "1", "2", "3", "4", "5", "6", "7" ]
223
2,259
1
false
The CYP27B1 gene is also expressed in extra renal sites, however the suppression of the gene by 1α,25(OH)2D3 has been described only in a few other cell lines derived from other tissues, such as colon-derived cells.
[ "6", "7" ]
The CYP27B1 gene is also expressed in extra renal sites, however the suppression of the gene by 1α,25(OH)2D3 has been described only in a few other cell lines derived from other tissues, such as colon-derived cells.
true
true
true
true
true
388
1
INTRODUCTION
1
8
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The effects of 1α,25(OH)2D3 are mediated via the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, to which 1α,25(OH)2D3 binds with high affinity.
[ "8", "9", "10–12", "4" ]
168
2,260
0
false
The effects of 1α,25(OH)2D3 are mediated via the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, to which 1α,25(OH)2D3 binds with high affinity.
[]
The effects of 1α,25(OH)2D3 are mediated via the vitamin D receptor (VDR), a member of the nuclear receptor superfamily, to which 1α,25(OH)2D3 binds with high affinity.
true
true
true
true
true
389
1
INTRODUCTION
1
8
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Responsiveness of a given gene to 1α,25(OH)2D3 requires that its regulatory regions contain a VDRE.
[ "8", "9", "10–12", "4" ]
99
2,261
0
false
Responsiveness of a given gene to 1α,25(OH)2D3 requires that its regulatory regions contain a VDRE.
[]
Responsiveness of a given gene to 1α,25(OH)2D3 requires that its regulatory regions contain a VDRE.
true
true
true
true
true
389
1
INTRODUCTION
1
8
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The VDREs of positively regulated genes are direct repeats of two hexameric-core-binding motifs spaced by 3 or 4 nt (DR3 or DR4, respectively) or everted repeats spaced by 6–9 nt (ER6 and ER9, respectively) (8,9).
[ "8", "9", "10–12", "4" ]
213
2,262
0
false
The VDREs of positively regulated genes are direct repeats of two hexameric-core-binding motifs spaced by 3 or 4 nt or everted repeats spaced by 6–9 nt.
[ "DR3 or DR4, respectively", "ER6 and ER9, respectively", "8,9" ]
The VDREs of positively regulated genes are direct repeats of two hexameric-core-binding motifs spaced by 3 or 4 nt or everted repeats spaced by 6–9 nt.
true
true
true
true
true
389
1
INTRODUCTION
1
8
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The hexameric sequences of the response elements of the primary 1α,25(OH)2D3 target genes usually have the consensus sequence RGKTSA (R = A or G, K = G or T, S = C or G).
[ "8", "9", "10–12", "4" ]
170
2,263
0
false
The hexameric sequences of the response elements of the primary 1α,25(OH)2D3 target genes usually have the consensus sequence RGKTSA (R = A or G, K = G or T, S = C or G).
[]
The hexameric sequences of the response elements of the primary 1α,25(OH)2D3 target genes usually have the consensus sequence RGKTSA (R = A or G, K = G or T, S = C or G).
true
true
true
true
true
389
1
INTRODUCTION
1
10–12
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The VDREs of most previously studied negatively regulated genes resemble those of positively regulated genes, although negative regulation may not necessarily require both VDRE half sites (10–12).
[ "8", "9", "10–12", "4" ]
196
2,264
1
false
The VDREs of most previously studied negatively regulated genes resemble those of positively regulated genes, although negative regulation may not necessarily require both VDRE half sites.
[ "10–12" ]
The VDREs of most previously studied negatively regulated genes resemble those of positively regulated genes, although negative regulation may not necessarily require both VDRE half sites.
true
true
true
true
true
389
1
INTRODUCTION
1
4
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The reported negative VDRE of the CYP27B1 is an exception, because it does not contain a consensus sequence (4).
[ "8", "9", "10–12", "4" ]
112
2,265
1
false
The reported negative VDRE of the CYP27B1 is an exception, because it does not contain a consensus sequence.
[ "4" ]
The reported negative VDRE of the CYP27B1 is an exception, because it does not contain a consensus sequence.
true
true
true
true
true
389
1
INTRODUCTION
1
8
[ "B8", "B9", "B10 B11 B12", "B4" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
In addition, the authors proposed that the regulation of the CYP27B1 gene involves an indirect binding of VDR to DNA, where VDR associates with the nVDRE ligand-dependently via another transcription factor, the VDR interacting repressor (VDIR).
[ "8", "9", "10–12", "4" ]
244
2,266
0
false
In addition, the authors proposed that the regulation of the CYP27B1 gene involves an indirect binding of VDR to DNA, where VDR associates with the nVDRE ligand-dependently via another transcription factor, the VDR interacting repressor (VDIR).
[]
In addition, the authors proposed that the regulation of the CYP27B1 gene involves an indirect binding of VDR to DNA, where VDR associates with the nVDRE ligand-dependently via another transcription factor, the VDR interacting repressor (VDIR).
true
true
true
true
true
389
2
INTRODUCTION
1
13
[ "B13", "B14", "B15", "B16", "B17", "B18" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
Binding of 1α,25(OH)2D3 causes a conformational change within the ligand-binding domain of the VDR, which modulates its interactions with nuclear proteins, such as coactivator (CoA) and corepressor (CoR) proteins (13).
[ "13", "14", "15", "16", "17", "18" ]
218
2,267
1
false
Binding of 1α,25(OH)2D3 causes a conformational change within the ligand-binding domain of the VDR, which modulates its interactions with nuclear proteins, such as coactivator (CoA) and corepressor (CoR) proteins.
[ "13" ]
Binding of 1α,25(OH)2D3 causes a conformational change within the ligand-binding domain of the VDR, which modulates its interactions with nuclear proteins, such as coactivator (CoA) and corepressor (CoR) proteins.
true
true
true
true
true
390
2
INTRODUCTION
1
14
[ "B13", "B14", "B15", "B16", "B17", "B18" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
CoR proteins, such as NCoR1 (14) and SMRT/NCoR2 (15), link non-liganded, DNA-bound VDR to enzymes with histone deacetylase activity that cause chromatin condensation (16).
[ "13", "14", "15", "16", "17", "18" ]
171
2,268
1
false
CoR proteins, such as NCoR1 and SMRT/NCoR2, link non-liganded, DNA-bound VDR to enzymes with histone deacetylase activity that cause chromatin condensation.
[ "14", "15", "16" ]
CoR proteins, such as NCoR1 and SMRT/NCoR2, link non-liganded, DNA-bound VDR to enzymes with histone deacetylase activity that cause chromatin condensation.
true
true
true
true
true
390
2
INTRODUCTION
1
17
[ "B13", "B14", "B15", "B16", "B17", "B18" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
The conformational change within VDR’s ligand-binding domain results in the replacement of a CoR by a CoA protein of the p160 family, such as SRC-1, SRC-2 or SRC-3 (17).
[ "13", "14", "15", "16", "17", "18" ]
169
2,269
1
false
The conformational change within VDR’s ligand-binding domain results in the replacement of a CoR by a CoA protein of the p160 family, such as SRC-1, SRC-2 or SRC-3.
[ "17" ]
The conformational change within VDR’s ligand-binding domain results in the replacement of a CoR by a CoA protein of the p160 family, such as SRC-1, SRC-2 or SRC-3.
true
true
true
true
true
390
2
INTRODUCTION
1
18
[ "B13", "B14", "B15", "B16", "B17", "B18" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
These CoAs link the ligand-activated VDR to enzymes displaying histone acetyltransferase (HAT) activity, such as CBP, that cause chromatin relaxation by their action on histone tails and thereby reversing the action of unliganded VDR (18).
[ "13", "14", "15", "16", "17", "18" ]
239
2,270
1
false
These CoAs link the ligand-activated VDR to enzymes displaying histone acetyltransferase (HAT) activity, such as CBP, that cause chromatin relaxation by their action on histone tails and thereby reversing the action of unliganded VDR.
[ "18" ]
These CoAs link the ligand-activated VDR to enzymes displaying histone acetyltransferase (HAT) activity, such as CBP, that cause chromatin relaxation by their action on histone tails and thereby reversing the action of unliganded VDR.
true
true
true
true
true
390
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Traditionally, VDREs are thought to locate relatively close to the TSS of 1α,25(OH)2D3 target genes.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
100
2,271
0
false
Traditionally, VDREs are thought to locate relatively close to the TSS of 1α,25(OH)2D3 target genes.
[]
Traditionally, VDREs are thought to locate relatively close to the TSS of 1α,25(OH)2D3 target genes.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
For example, both human and rat vitamin D 24-hydroxylase (CYP24) genes have a cluster of VDREs in their proximal promoters (approximate position −140 to −300) (19–22).
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
167
2,272
1
false
For example, both human and rat vitamin D 24-hydroxylase genes have a cluster of VDREs in their proximal promoters.
[ "CYP24", "approximate position −140 to −300", "19–22" ]
For example, both human and rat vitamin D 24-hydroxylase genes have a cluster of VDREs in their proximal promoters.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
However, recently several promoter studies have revealed that the gene promoters may contain multiple response elements that locate not only within proximal promoters but also in more distal regions (23,24) and even within coding regions (25,26).
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
246
2,273
0
false
However, recently several promoter studies have revealed that the gene promoters may contain multiple response elements that locate not only within proximal promoters but also in more distal regions and even within coding regions.
[ "23,24", "25,26" ]
However, recently several promoter studies have revealed that the gene promoters may contain multiple response elements that locate not only within proximal promoters but also in more distal regions and even within coding regions.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
These studies have so far concerned with only positively regulated genes.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
73
2,274
0
false
These studies have so far concerned with only positively regulated genes.
[]
These studies have so far concerned with only positively regulated genes.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
This raises a question, whether negatively regulated genes also have multiple response elements.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
96
2,275
0
false
This raises a question, whether negatively regulated genes also have multiple response elements.
[]
This raises a question, whether negatively regulated genes also have multiple response elements.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Since the promoter studies of the human CYP27B1 gene have so far been limited to the first 1.7 kb upstream of the TSS (4,27–29), in this study, we have extended the promoter analysis further upstream and examined the role of distal promoter regions to the regulation of the human CYP27B1 gene by 1α,25(OH)2D3.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
309
2,276
0
false
Since the promoter studies of the human CYP27B1 gene have so far been limited to the first 1.7 kb upstream of the TSS, in this study, we have extended the promoter analysis further upstream and examined the role of distal promoter regions to the regulation of the human CYP27B1 gene by 1α,25(OH)2D3.
[ "4,27–29" ]
Since the promoter studies of the human CYP27B1 gene have so far been limited to the first 1.7 kb upstream of the TSS, in this study, we have extended the promoter analysis further upstream and examined the role of distal promoter regions to the regulation of the human CYP27B1 gene by 1α,25(OH)2D3.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
We analyzed 13 contiguous genomic regions spanning 5.4 kb of the CYP27B1 promoter by chromatin immunoprecipitation (ChIP) scanning.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
131
2,277
0
false
We analyzed 13 contiguous genomic regions spanning 5.4 kb of the CYP27B1 promoter by chromatin immunoprecipitation (ChIP) scanning.
[]
We analyzed 13 contiguous genomic regions spanning 5.4 kb of the CYP27B1 promoter by chromatin immunoprecipitation (ChIP) scanning.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Our studies revealed two new 1α,25(OH)2D3-responsive regions in the distal promoter 2.6 and 3.2 kb upstream from the TSS.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
121
2,278
0
false
Our studies revealed two new 1α,25(OH)2D3-responsive regions in the distal promoter 2.6 and 3.2 kb upstream from the TSS.
[]
Our studies revealed two new 1α,25(OH)2D3-responsive regions in the distal promoter 2.6 and 3.2 kb upstream from the TSS.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Interestingly, in contrast to the nVDRE-containing region, in silico screening revealed that both of the new 1α,25(OH)2D3-responsive regions contained classical VDRE sequences that were shown to directly bind VDR–retinoid X receptor (RXR) heterodimers in a ligand-dependent manner, when studied by gel shift assays.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
315
2,279
0
false
Interestingly, in contrast to the nVDRE-containing region, in silico screening revealed that both of the new 1α,25(OH)2D3-responsive regions contained classical VDRE sequences that were shown to directly bind VDR–retinoid X receptor (RXR) heterodimers in a ligand-dependent manner, when studied by gel shift assays.
[]
Interestingly, in contrast to the nVDRE-containing region, in silico screening revealed that both of the new 1α,25(OH)2D3-responsive regions contained classical VDRE sequences that were shown to directly bind VDR–retinoid X receptor (RXR) heterodimers in a ligand-dependent manner, when studied by gel shift assays.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Extensive ChIP analysis suggested that the new regions have a number of similarities with the established nVDRE in the recruitment of different cofactors, as well as recruiting both VDR and RXR, supporting the idea that the putative VDREs are functional.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
254
2,280
0
false
Extensive ChIP analysis suggested that the new regions have a number of similarities with the established nVDRE in the recruitment of different cofactors, as well as recruiting both VDR and RXR, supporting the idea that the putative VDREs are functional.
[]
Extensive ChIP analysis suggested that the new regions have a number of similarities with the established nVDRE in the recruitment of different cofactors, as well as recruiting both VDR and RXR, supporting the idea that the putative VDREs are functional.
true
true
true
true
true
391
3
INTRODUCTION
1
19–22
[ "B19 B20 B21 B22", "B23", "B24", "B25", "B26", "B4", "B27 B28 B29" ]
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
In addition, chromatin conformation capture (3C) analysis suggested that the new regions are directly connected with the TSS via chromatin looping in a ligand-dependent and cell-specific manner.
[ "19–22", "23", "24", "25", "26", "4", "27–29" ]
194
2,281
0
false
In addition, chromatin conformation capture (3C) analysis suggested that the new regions are directly connected with the TSS via chromatin looping in a ligand-dependent and cell-specific manner.
[]
In addition, chromatin conformation capture (3C) analysis suggested that the new regions are directly connected with the TSS via chromatin looping in a ligand-dependent and cell-specific manner.
true
true
true
true
true
391
0
DISCUSSION
1
4
[ "B4" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
The mechanism of negative gene regulation by nuclear receptors is still poorly understood, but the human CYP27B1 gene and its down-regulation in the presence of 1α,25(OH)2D3 may be so far the most detailed model (4).
[ "4" ]
216
2,282
1
false
The mechanism of negative gene regulation by nuclear receptors is still poorly understood, but the human CYP27B1 gene and its down-regulation in the presence of 1α,25(OH)2D3 may be so far the most detailed model.
[ "4" ]
The mechanism of negative gene regulation by nuclear receptors is still poorly understood, but the human CYP27B1 gene and its down-regulation in the presence of 1α,25(OH)2D3 may be so far the most detailed model.
true
true
true
true
true
392
0
DISCUSSION
1
4
[ "B4" ]
17,426,122
pmid-12637589|pmid-8845856|pmid-4330040|pmid-15934135|NA|pmid-16081283|NA|pmid-15934135
Since the model takes account only the proximal promoter of the CYP27B1 gene, we aimed in this study to test the hypothesis that also in the case of gene repression multiple response elements located in more distal regions may be involved in the regulation.
[ "4" ]
257
2,283
0
false
Since the model takes account only the proximal promoter of the CYP27B1 gene, we aimed in this study to test the hypothesis that also in the case of gene repression multiple response elements located in more distal regions may be involved in the regulation.
[]
Since the model takes account only the proximal promoter of the CYP27B1 gene, we aimed in this study to test the hypothesis that also in the case of gene repression multiple response elements located in more distal regions may be involved in the regulation.
true
true
true
true
true
392
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
The distance between the TSSs of the neighboring genes CYP27B1 and METTL1 is only 5.4 kb (Figure 2A), with the METTL1 gene being read in the same direction as CYP27B1 (its last exon ends only 1.2 kb upstream of the TSS of the CYP27B1gene).
[ "4", "27–29" ]
239
2,284
0
false
The distance between the TSSs of the neighboring genes CYP27B1 and METTL1 is only 5.4 kb (Figure 2A), with the METTL1 gene being read in the same direction as CYP27B1 (its last exon ends only 1.2 kb upstream of the TSS of the CYP27B1gene).
[]
The distance between the TSSs of the neighboring genes CYP27B1 and METTL1 is only 5.4 kb (Figure 2A), with the METTL1 gene being read in the same direction as CYP27B1 (its last exon ends only 1.2 kb upstream of the TSS of the CYP27B1gene).
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Thus, the promoter of CYP27B1 seems to be only 1.2 kb in size.
[ "4", "27–29" ]
62
2,285
0
false
Thus, the promoter of CYP27B1 seems to be only 1.2 kb in size.
[]
Thus, the promoter of CYP27B1 seems to be only 1.2 kb in size.
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Indeed, the studies of human and mouse CYP27B1 promoters have so far considered only the first 1.7 kb upstream from the TSS of CYP27B1 (4,27–29).
[ "4", "27–29" ]
145
2,286
0
false
Indeed, the studies of human and mouse CYP27B1 promoters have so far considered only the first 1.7 kb upstream from the TSS of CYP27B1.
[ "4,27–29" ]
Indeed, the studies of human and mouse CYP27B1 promoters have so far considered only the first 1.7 kb upstream from the TSS of CYP27B1.
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Therefore, it is interesting that the combined results of our in silico screening and promoter ChIP scanning suggested that within the studied CYP27B1 promoter region, two additional VDREs, located in regions 7 and 9 (being within introns of the METTL1 gene) upstream from region 2 carrying the nVDRE.
[ "4", "27–29" ]
301
2,287
0
false
Therefore, it is interesting that the combined results of our in silico screening and promoter ChIP scanning suggested that within the studied CYP27B1 promoter region, two additional VDREs, located in regions 7 and 9 (being within introns of the METTL1 gene) upstream from region 2 carrying the nVDRE.
[]
Therefore, it is interesting that the combined results of our in silico screening and promoter ChIP scanning suggested that within the studied CYP27B1 promoter region, two additional VDREs, located in regions 7 and 9 (being within introns of the METTL1 gene) upstream from region 2 carrying the nVDRE.
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
According to our ChIP scanning of the CYP27B1 promoter, the time-dependent binding profile of VDR was similar both in MCF-7 cells and HEK-293 cells with one exception.
[ "4", "27–29" ]
167
2,288
0
false
According to our ChIP scanning of the CYP27B1 promoter, the time-dependent binding profile of VDR was similar both in MCF-7 cells and HEK-293 cells with one exception.
[]
According to our ChIP scanning of the CYP27B1 promoter, the time-dependent binding profile of VDR was similar both in MCF-7 cells and HEK-293 cells with one exception.
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
In HEK-293 cells, the VDR seemed to associate with the described CYP27B1 gene TSS stronger than in MCF-7 cells (Figure 2).
[ "4", "27–29" ]
122
2,289
0
false
In HEK-293 cells, the VDR seemed to associate with the described CYP27B1 gene TSS stronger than in MCF-7 cells (Figure 2).
[]
In HEK-293 cells, the VDR seemed to associate with the described CYP27B1 gene TSS stronger than in MCF-7 cells (Figure 2).
true
true
true
true
true
393
1
DISCUSSION
1
4
[ "B4", "B27 B28 B29" ]
17,426,122
pmid-9673449|pmid-10677278|pmid-1325645|pmid-8776727|pmid-8663213|pmid-15934135|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Since region 1 possesses neither an nVDRE nor a regular VDRE, this may suggest that the protein bridge exists between the VDR-binding regions and the TSS in HEK-293, but not in MCF-7 cells.
[ "4", "27–29" ]
189
2,290
0
false
Since region 1 possesses neither an nVDRE nor a regular VDRE, this may suggest that the protein bridge exists between the VDR-binding regions and the TSS in HEK-293, but not in MCF-7 cells.
[]
Since region 1 possesses neither an nVDRE nor a regular VDRE, this may suggest that the protein bridge exists between the VDR-binding regions and the TSS in HEK-293, but not in MCF-7 cells.
true
true
true
true
true
393
2
DISCUSSION
1
4
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
According to Murayama and colleagues (4), the association of the VDR–RXR heterodimer to the nVDRE is not a direct binding to DNA, but occurs via the transcription factor VDIR.
[ "4", "10–12" ]
175
2,291
1
false
According to Murayama and colleagues, the association of the VDR–RXR heterodimer to the nVDRE is not a direct binding to DNA, but occurs via the transcription factor VDIR.
[ "4" ]
According to Murayama and colleagues, the association of the VDR–RXR heterodimer to the nVDRE is not a direct binding to DNA, but occurs via the transcription factor VDIR.
true
true
true
true
true
394
2
DISCUSSION
1
4
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
We found that in vitro-translated VDR–RXR heterodimers cannot bind to the nVDRE although in vitro-translated VDIR can (Figure 3).
[ "4", "10–12" ]
129
2,292
0
false
We found that in vitro-translated VDR–RXR heterodimers cannot bind to the nVDRE although in vitro-translated VDIR can (Figure 3).
[]
We found that in vitro-translated VDR–RXR heterodimers cannot bind to the nVDRE although in vitro-translated VDIR can (Figure 3).
true
true
true
true
true
394
2
DISCUSSION
1
4
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
Interestingly, with the distal VDREs, reasonable VDR–RXR heterodimer association could be observed with VDRE1 and VDRE2 from regions 7 and 9, respectively.
[ "4", "10–12" ]
155
2,293
0
false
Interestingly, with the distal VDREs, reasonable VDR–RXR heterodimer association could be observed with VDRE1 and VDRE2 from regions 7 and 9, respectively.
[]
Interestingly, with the distal VDREs, reasonable VDR–RXR heterodimer association could be observed with VDRE1 and VDRE2 from regions 7 and 9, respectively.
true
true
true
true
true
394
2
DISCUSSION
1
4
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
This did not apply to the neighboring VDRE3, suggesting that VDR is associated only with VDRE2 within region 9.
[ "4", "10–12" ]
111
2,294
0
false
This did not apply to the neighboring VDRE3, suggesting that VDR is associated only with VDRE2 within region 9.
[]
This did not apply to the neighboring VDRE3, suggesting that VDR is associated only with VDRE2 within region 9.
true
true
true
true
true
394
2
DISCUSSION
1
4
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
The binding of the VDR–RXR complex to VDRE1 and VDRE2 was ligand dependent, but contrary to that of nVDRE, the binding may involve direct interactions with DNA sequences.
[ "4", "10–12" ]
170
2,295
0
false
The binding of the VDR–RXR complex to VDRE1 and VDRE2 was ligand dependent, but contrary to that of nVDRE, the binding may involve direct interactions with DNA sequences.
[]
The binding of the VDR–RXR complex to VDRE1 and VDRE2 was ligand dependent, but contrary to that of nVDRE, the binding may involve direct interactions with DNA sequences.
true
true
true
true
true
394
2
DISCUSSION
1
10–12
[ "B4", "B10 B11 B12" ]
17,426,122
pmid-10322133|pmid-7566127|pmid-7566114|pmid-10877839|pmid-16094445|pmid-11559745|pmid-15934135|pmid-1325645|pmid-8776727|pmid-8663213
Therefore, the new distal VDREs resemble positive VDREs, as has been previously described for most of the negative VDREs identified so far (10–12).
[ "4", "10–12" ]
147
2,296
1
false
Therefore, the new distal VDREs resemble positive VDREs, as has been previously described for most of the negative VDREs identified so far.
[ "10–12" ]
Therefore, the new distal VDREs resemble positive VDREs, as has been previously described for most of the negative VDREs identified so far.
true
true
true
true
true
394
3
DISCUSSION
0
null
null
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
A reporter gene analysis of different CYP27B1 promoter fragments (Figure 4) showed that both the regions containing the nVDRE and VDRE2/3 were able to repress gene activity in HEK-293 cells, but not in MCF-7 cells.
null
214
2,297
0
false
null
null
A reporter gene analysis of different CYP27B1 promoter fragments (Figure 4) showed that both the regions containing the nVDRE and VDRE2/3 were able to repress gene activity in HEK-293 cells, but not in MCF-7 cells.
true
true
true
true
true
395
3
DISCUSSION
0
null
null
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
In addition, a longer promoter fragment including both the nVDRE and VDRE2/3, an even more significant repression was achieved.
null
127
2,298
0
false
null
null
In addition, a longer promoter fragment including both the nVDRE and VDRE2/3, an even more significant repression was achieved.
true
true
true
true
true
395
3
DISCUSSION
0
null
null
17,426,122
pmid-7632726|pmid-8036172|pmid-8060315|pmid-7829502|pmid-15863722|pmid-15919092|pmid-16186133|pmid-16497728|pmid-15934135|pmid-15691891|pmid-15243130|pmid-9465024
Therefore, our results suggest that both nVDRE and VDRE2/3 are efficient negative regulators of the CYP27B1 promoter and work in HEK-293 cells together in the repression of CYP27B1 gene expression.
null
197
2,299
0
false
null
null
Therefore, our results suggest that both nVDRE and VDRE2/3 are efficient negative regulators of the CYP27B1 promoter and work in HEK-293 cells together in the repression of CYP27B1 gene expression.
true
true
true
true
true
395