Differential activity by DNA-induced quarternary structures of POU transcription factors

A. Reményi, Alexey Tomilin, Hans R. Schöler, Matthias Wilmanns

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 languageEnglish
Pages (from-to)979-984
Number of pages6
JournalBiochemical Pharmacology
Volume64
Issue number5-6
DOIs
Publication statusPublished - Sep 1 2002

Fingerprint

POU Domain Factors
DNA
Conformations
Nucleotide Motifs
Binding Sites
Transcription Factor Pit-1
Octamer Transcription Factor-1
Transcription Factors
Dimers
Crystal structure
Response Elements
Base Pairing
Transcription

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 journalArticle

Reményi, A. ; Tomilin, Alexey ; Schöler, Hans R. ; Wilmanns, Matthias. / Differential activity by DNA-induced quarternary structures of POU transcription factors. In: Biochemical Pharmacology. 2002 ; Vol. 64, No. 5-6. pp. 979-984.
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