Transcriptional anti-repression. Thyroid hormone receptor β-2 recruits SMRT corepressor but interferes with subsequent assembly of a functional corepressor complex

Zhihong Yang, Suk Hyun Hong, Martin L. Privalsky

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Thyroid hormone receptors (T3Rs) are hormone-regulated transcription factors. Different T3R isoforms are expressed in a tissue-specific and developmentally regulated manner. The T3Rα-1, β-0, and β-1 isoforms typically repress target gene expression in the absence of hormone and activate transcription in the presence of hormone. Intriguingly, however, the T3Rβ-2 isoform fails to repress, and instead is able to activate transcription in both the absence and presence of hormone. We investigated the molecular mechanism behind this absence of repression by T3Rβ-2. Repression by T3Rα-1, β-0, and β-1 is mediated by the ability of these isoforms to physically recruit a SMRT/N-CoR corepressor complex. We determined that the unliganded T3Rβ-2 also recruits the SMRT corepressor; in contrast to the α-1, β-0, and β-1 isoforms, however, the T3Rβ-2 protein interacts not only with the C-terminal 'receptor-interaction domain' of SMRT, but also makes additional contacts with the N-terminal 'silencing domain' of the SMRT corepressor. These additional, T3Rβ-2-specific contacts interfere with the subsequent association of SMRT with mSin3, a crucial second subunit of the corepressor holocomplex. Our results suggest that T3Rβ-2 regulates transcription through a novel anti-repression mechanism, recruiting SMRT, but preventing the subsequent formation of a functional corepressor complex.

Original languageEnglish (US)
Pages (from-to)37131-37138
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number52
DOIs
StatePublished - Dec 24 1999

ASJC Scopus subject areas

  • Biochemistry

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