The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor

Theresa Alenghat, Jiujiu Yu, Mitchell A. Lazar

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Unliganded thyroid hormone receptor (TR) actively represses transcription via the nuclear receptor corepressor (N-CoR)/histone deacetylase 3 (HDAC3) complex. Although transcriptional activation by liganded receptors involves chromatin remodeling, the role of ATP-dependent remodeling in receptor-mediated repression is unknown. Here we report that SNF2H, the mammalian ISWI chromatin remodeling ATPase, is critical for repression of a genomically integrated, TR-regulated reporter gene. N-CoR and HDAC3 are both required for recruitment of SNF2H to the repressed gene. SNF2H does not interact directly with the N-CoR/HDAC3 complex, but binds to unacetylated histone H4 tails, suggesting that deacetylase activity of the corepressor complex is critical to SNF2H function. Indeed, HDAC3 as well as SNF2H are required for nucleosomal organization on the TR target gene. Consistent with these findings, reduction of SNF2H induces expression of an endogenous TR-regulated gene, dio1, in liver cells. Thus, although not apparent from studies of transiently transfected reporter genes, gene repression by TR involves the targeting of chromatin remodeling factors to repressed genes by the HDAC activity of nuclear receptor corepressors.

Original languageEnglish (US)
Pages (from-to)3966-3974
Number of pages9
JournalEMBO Journal
Volume25
Issue number17
DOIs
StatePublished - Sep 6 2006

Fingerprint

Thyroid Hormone Receptors
Co-Repressor Proteins
Chromatin
Genes
Chromatin Assembly and Disassembly
Histone Deacetylases
Reporter Genes
Histones
Transcriptional Activation
Adenosine Triphosphatases
Adenosine Triphosphate
Transcription
Liver
histone deacetylase 3
Chemical activation

Keywords

  • Chromatin
  • HDAC
  • Nuclear receptor
  • Repression
  • SNF2H

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor. / Alenghat, Theresa; Yu, Jiujiu; Lazar, Mitchell A.

In: EMBO Journal, Vol. 25, No. 17, 06.09.2006, p. 3966-3974.

Research output: Contribution to journalArticle

Alenghat, Theresa ; Yu, Jiujiu ; Lazar, Mitchell A. / The N-CoR complex enables chromatin remodeler SNF2H to enhance repression by thyroid hormone receptor. In: EMBO Journal. 2006 ; Vol. 25, No. 17. pp. 3966-3974.
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