Abstract
Recent structural studies on transcription factors from the POU family in complex with multiple cognate DNA enhancer elements have established a novel concept in DNA-mediated formation of distinct conformations of transcription regulator assemblies. Two crystal structures of the Oct-1 transcription factor in the presence of two different DNA sites have demonstrated how its POU DNA-binding segment is capable in forming two unrelated dimer arrangements, which is DNA motif dependent. While one arrangement allows binding of the Oct-1 specific coactivator OBF-1, binding of this coactivator is blocked in the second arrangement because the binding site is involved in its own dimer assembly. Conversely, two crystal structures of another POU transcription factor, Pit-1, have demonstrated how the same overall assembly is maintained in the presence of two different DNA response elements. However, since the distance of the two Pit-1 half-binding sites on these elements differ by two base pairs, the overall dimensions of the two complexes vary, allowing binding of a specific represssor (N-CoR) in one conformation but not in the other. Thus, despite the occurrence of different DNA-mediated molecular mechanisms, the net result, conformation-dependent binding of further regulators, is equivalent. These data introduce a concept where the DNA motif not only serves as binding site for specific transcription factors but also regulates their function by mediating specific transcription factor assemblies, which determine binding to conformation-dependent coregulators.
| Original language | English |
|---|---|
| Pages (from-to) | 979-984 |
| Number of pages | 6 |
| Journal | Biochemical Pharmacology |
| Volume | 64 |
| Issue number | 5-6 |
| DOIs | |
| Publication status | Published - Sep 1 2002 |
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Keywords
- Coregulator
- Differential function
- POU transcription factor
- Quarternary arrangement
- Regulation
ASJC Scopus subject areas
- Pharmacology
Cite this
Differential activity by DNA-induced quarternary structures of POU transcription factors. / Reményi, A.; Tomilin, Alexey; Schöler, Hans R.; Wilmanns, Matthias.
In: Biochemical Pharmacology, Vol. 64, No. 5-6, 01.09.2002, p. 979-984.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential activity by DNA-induced quarternary structures of POU transcription factors
AU - Reményi, A.
AU - Tomilin, Alexey
AU - Schöler, Hans R.
AU - Wilmanns, Matthias
PY - 2002/9/1
Y1 - 2002/9/1
N2 - Recent structural studies on transcription factors from the POU family in complex with multiple cognate DNA enhancer elements have established a novel concept in DNA-mediated formation of distinct conformations of transcription regulator assemblies. Two crystal structures of the Oct-1 transcription factor in the presence of two different DNA sites have demonstrated how its POU DNA-binding segment is capable in forming two unrelated dimer arrangements, which is DNA motif dependent. While one arrangement allows binding of the Oct-1 specific coactivator OBF-1, binding of this coactivator is blocked in the second arrangement because the binding site is involved in its own dimer assembly. Conversely, two crystal structures of another POU transcription factor, Pit-1, have demonstrated how the same overall assembly is maintained in the presence of two different DNA response elements. However, since the distance of the two Pit-1 half-binding sites on these elements differ by two base pairs, the overall dimensions of the two complexes vary, allowing binding of a specific represssor (N-CoR) in one conformation but not in the other. Thus, despite the occurrence of different DNA-mediated molecular mechanisms, the net result, conformation-dependent binding of further regulators, is equivalent. These data introduce a concept where the DNA motif not only serves as binding site for specific transcription factors but also regulates their function by mediating specific transcription factor assemblies, which determine binding to conformation-dependent coregulators.
AB - Recent structural studies on transcription factors from the POU family in complex with multiple cognate DNA enhancer elements have established a novel concept in DNA-mediated formation of distinct conformations of transcription regulator assemblies. Two crystal structures of the Oct-1 transcription factor in the presence of two different DNA sites have demonstrated how its POU DNA-binding segment is capable in forming two unrelated dimer arrangements, which is DNA motif dependent. While one arrangement allows binding of the Oct-1 specific coactivator OBF-1, binding of this coactivator is blocked in the second arrangement because the binding site is involved in its own dimer assembly. Conversely, two crystal structures of another POU transcription factor, Pit-1, have demonstrated how the same overall assembly is maintained in the presence of two different DNA response elements. However, since the distance of the two Pit-1 half-binding sites on these elements differ by two base pairs, the overall dimensions of the two complexes vary, allowing binding of a specific represssor (N-CoR) in one conformation but not in the other. Thus, despite the occurrence of different DNA-mediated molecular mechanisms, the net result, conformation-dependent binding of further regulators, is equivalent. These data introduce a concept where the DNA motif not only serves as binding site for specific transcription factors but also regulates their function by mediating specific transcription factor assemblies, which determine binding to conformation-dependent coregulators.
KW - Coregulator
KW - Differential function
KW - POU transcription factor
KW - Quarternary arrangement
KW - Regulation
UR - http://www.scopus.com/inward/record.url?scp=0036710562&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036710562&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(02)01164-4
DO - 10.1016/S0006-2952(02)01164-4
M3 - Article
C2 - 12213595
AN - SCOPUS:0036710562
VL - 64
SP - 979
EP - 984
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 5-6
ER -