Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3

Jiwen Li, Jin Wang, Jianxiang Wang, Zafar Nawaz, Johnson M. Liu, Jun Qin, Jiemin Wong

Research output: Contribution to journalArticle

467 Scopus citations

Abstract

We present evidence that both corepressors SMRT and N-CoR exist in large protein complexes with estimated sizes of 1.5-2 MDa in HeLa nuclear extracts. Using a combination of conventional and immunoaffinity chromatography, we have successfully isolated a SMRT complex and identified histone deacetylase 3 (HDAC3) and transducin (β)-like I (TBL1), a WD-40 repeat-containing protein, as the subunits of the purified SMRT complex. We show that the HDAC3-containing SMRT and N-CoR complexes can bind to unliganded thyroid hormone receptors (TRs) in vitro. We demonstrate further that in Xenopus oocytes, both SMRT and N-CoR also associate with HDAC3 in large protein complexes and that injection of antibodies against HDAC3 or SMRT\N-CoR led to a partial relief of repression by unliganded TR/RXR. These findings thus establish both SMRT and N-CoR complexes as bona fide HDAC-containing complexes and shed new light on the molecular pathways by which N-CoR and SMRT function in transcriptional repression.

Original languageEnglish (US)
Pages (from-to)4342-4350
Number of pages9
JournalEMBO Journal
Volume19
Issue number16
DOIs
StatePublished - Aug 15 2000

Keywords

  • HDAC3
  • Repression
  • SMRT and N-CoR corepressor complexes
  • TBL1

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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