Coactivator recruitment is enhanced by thyroid hormone receptor trimers

Brenda J. Mengeling, Sangho Lee, Martin L. Privalsky

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Thyroid hormone receptors (TRs) are hormone-regulated transcription factors. TRs are generally thought to bind to their DNA target sites as homodimers or as TR/retinoid X receptor (RXR) heterodimers. However, we have shown that certain TR isoforms, such as TRβ0, can bind as trimers to a subset of naturally occurring DNA elements. We report here that this trimeric mode of DNA recognition by TRβ0 also results in an enhanced recruitment of coactivators in vitro and increased transcriptional activation in cells compared to TRβ0 dimers. At least part of this enhanced coactivator recruitment reflects a selectively enhanced avidity of the TRβ0 trimer for a specific LXXLL interaction motif within the p160 coactivators. TRβ0 trimers also recruit certain coactivators at lower concentrations of T3 hormone and exhibit distinct coactivator stoichiometries than do TRβ0 dimers. We conclude that trimer formation confers isoform-specific DNA recognition and transcriptional regulatory properties that are not observed for TR dimers.

Original languageEnglish (US)
Pages (from-to)47-62
Number of pages16
JournalMolecular and Cellular Endocrinology
Volume280
Issue number1-2
DOIs
StatePublished - Jan 2 2008

Keywords

  • Coactivator
  • Coregualtor recruitment
  • Thyroid hormone receptor
  • Transcriptional activation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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