DNA-looping by RXR tetramers permits transcriptional regulation "at a distance"

Rubina Yasmin, Kay T. Yeung, Richard H. Chung, Maria E. Gaczynska, Pawel A. Osmulski, Noa Noy

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

RXR, a member of the superfamily of nuclear hormone receptors, regulates gene transcription in response to 9-cis-retinoic acid. We previously showed that, among nuclear receptors, RXR is unique in that it self-associates into homotetramers, and that these tetramers dissociate rapidly upon ligation. Here, we report that binding of RXR tetramers to DNA containing two RXR response elements results in a dramatic DNA-looping. RXR can thus juxtapose distant DNA sequences, enabling transcriptional regulation by far-upstream factors. We show that RXR functions as a DNA architectural factor and that, while this activity is regulated by 9-cis-retinoic acid, it is distinct from and independent of the receptor's intrinsic transcriptional activity. The data establish RXR as the first identified architectural factor whose activity is regulated by a small ligand, and demonstrate a novel mechanism of transcriptional regulation by retinoids.

Original languageEnglish (US)
Pages (from-to)327-338
Number of pages12
JournalJournal of Molecular Biology
Volume343
Issue number2
DOIs
StatePublished - Oct 15 2004

Keywords

  • DNA-looping
  • RXR
  • nuclear receptor
  • retinoic acid
  • transcription

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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