Cooperative formation of high-order oligomers by retinoid X receptors

An unexpected mode of DNA recognition

Hongwu Chen, Martin L. Privalsky

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Nuclear hormone receptors are ligand-regulated transcription factors that function in metazoan homeostasis and differentiation. We report here that DNA recognition by at least one class of nuclear receptors, the retinoid X receptors (RXRs), can occur through an unanticipated mechanism involving the cooperative formation of protein tetramers and other high-order oligomers. Formation of these oligomeric complexes enables RXRs α and γ, but not β, to efficiently regulate transcription through response elements poorly recognized by RXR dimers. Thus, oligomer formation plays an important role in determining the specificity of DNA recognition by nuclear receptors and contributes to isoform-dependent differences in gene regulation.

Original languageEnglish (US)
Pages (from-to)422-426
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number2
DOIs
StatePublished - Jan 17 1995

Fingerprint

Retinoid X Receptors
Cytoplasmic and Nuclear Receptors
DNA
Response Elements
Protein Isoforms
Homeostasis
Transcription Factors
Ligands
Genes
Proteins

Keywords

  • CRBP II element
  • nuclear hormone receptors
  • retinoid X response element

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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N2 - Nuclear hormone receptors are ligand-regulated transcription factors that function in metazoan homeostasis and differentiation. We report here that DNA recognition by at least one class of nuclear receptors, the retinoid X receptors (RXRs), can occur through an unanticipated mechanism involving the cooperative formation of protein tetramers and other high-order oligomers. Formation of these oligomeric complexes enables RXRs α and γ, but not β, to efficiently regulate transcription through response elements poorly recognized by RXR dimers. Thus, oligomer formation plays an important role in determining the specificity of DNA recognition by nuclear receptors and contributes to isoform-dependent differences in gene regulation.

AB - Nuclear hormone receptors are ligand-regulated transcription factors that function in metazoan homeostasis and differentiation. We report here that DNA recognition by at least one class of nuclear receptors, the retinoid X receptors (RXRs), can occur through an unanticipated mechanism involving the cooperative formation of protein tetramers and other high-order oligomers. Formation of these oligomeric complexes enables RXRs α and γ, but not β, to efficiently regulate transcription through response elements poorly recognized by RXR dimers. Thus, oligomer formation plays an important role in determining the specificity of DNA recognition by nuclear receptors and contributes to isoform-dependent differences in gene regulation.

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