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EMBO J. 2000 Aug 15;19(16):4342-50.

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

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  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

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 (beta)-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.

PMID:
10944117
[PubMed - indexed for MEDLINE]
PMCID:
PMC302030
Free PMC Article
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