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PMID: 10640275 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nuclear receptor corepressors partner with class II histone deacetylases in a Sin3-independent repression pathway.

Genes & development ·Vol. 14 ·No. 1 ·2000-01-01 ·Pages 45-54

Huang EY, Zhang J, Miska EA, Guenther MG, Kouzarides T, Lazar MA

Abstract

Transcriptional repression mediated by corepressors N-CoR and SMRT is a critical function of nuclear hormone receptors, and is dysregulated in human myeloid leukemias. At the present time, these corepressors are thought to act exclusively through an mSin3/HDAC1 complex. Surprisingly, however, numerous biochemical studies have not detected N-CoR or SMRT in mSin3- and HDAC1-containing complexes. Each corepressor contains multiple repression domains (RDs), the significance of which is unknown. Here we show that these RDs are nonredundant, and that one RD, which is conserved in N-CoR and SMRT, represses transcription by interacting directly with class II HDAC4 and HDAC5. Endogenous N-CoR and SMRT each associate with HDAC4 in a complex that does not contain mSin3A or HDAC1. This is the first example of a single corepressor utilizing distinct domains to engage multiple HDAC complexes. The alternative HDAC complexes may mediate specific repression pathways in normal as well as leukemic cells.

MeSH Terms
Catalytic Domain Cell Line Histone Deacetylases/metabolism Humans Precipitin Tests Protein Binding Receptors, Cytoplasmic and Nuclear/metabolism Repressor Proteins/metabolism Saccharomyces cerevisiae Proteins Transcription Factors/metabolism
Chemicals
Receptors, Cytoplasmic and Nuclear Repressor Proteins SIN3 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcription Factors Histone Deacetylases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Huang E Y
Division of Endocrinology, Diabetes, and Metabolism, Departments of Medicine and Genetics, and The Penn Diabetes Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 USA.
Zhang J
Miska E A
Guenther M G
Kouzarides T
Lazar M A
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2000-01-01
Pages
45-54
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316335
Subset
IM
Grants
NIDDK NIH HHS · DK45586 · United States
NIDDK NIH HHS · R01 DK045586 · United States
NIDDK NIH HHS · P30 DK050306 · United States
NIDDK NIH HHS · DK43806 · United States
NIDDK NIH HHS · P30 DK50306 · United States
NIDDK NIH HHS · R37 DK043806 · United States
NIDDK NIH HHS · P30 DK019525 · United States
External Links
PubMed source PMC Full Text View journal details
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