Identification of mammalian Sds3 as an integral component of the Sin3/histone deacetylase corepressor complex

Leila Alland, Gregory David, Hong Shen-Li, Jason Potes, Rebecca Muhle, Hye Chun Lee, Harry Hou, Ken Chen, Ronald A. DePinho

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Silencing of gene transcription involves local chromatin modification achieved through the local recruitment of large multiprotein complexes containing histone deacetylase (HDAC) activity. The mammalian corepressors mSin3A and mSin3B have been shown to play a key role in this process by tethering HDACs 1 and 2 to promoter-bound transcription factors. Similar mechanisms appear to be operative in yeast, in which epistasis experiments have established that the mSin3 and HDAC orthologs (SIN3 and RPD3), along with a novel protein, SDS3, function in the same repressor pathway. Here, we report the identification of a component of the mSin3-HDAC complex that bears homology to yeast SDS3, physically associates with mSin3 proteins in vivo, represses transcription in a manner that is partially dependent on HDAC activity, and enables HDAC1 catalytic activity in vivo. That key physical and functional properties are also shared by yeast SDS3 underscores the central role of the Sin3-HDAC-Sds3 complex in eukaryotic cell biology, and the discovery of mSds3 in mammalian cells provides a new avenue for modulating the activity of this complex in human disease.

Original languageEnglish (US)
Pages (from-to)2743-2750
Number of pages8
JournalMolecular and cellular biology
Volume22
Issue number8
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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