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Molecular and Cellular Biology, April 2002, p. 2743-2750, Vol. 22, No. 8
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.8.2743-2750.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification of Mammalian Sds3 as an Integral Component of the Sin3/Histone Deacetylase Corepressor Complex

Leila Alland,1,{dagger} Gregory David,2 Hong Shen-Li,3 Jason Potes,1 Rebecca Muhle,1 Hye-Chun Lee,3 Harry Hou, Jr.,3 Ken Chen,3 and Ronald A. DePinho2*

Department of Pediatrics,1 Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,3 Departments of Adult Oncology, Medicine and Genetics, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 021152

Received 7 November 2001/ Returned for modification 18 December 2001/ Accepted 15 January 2002

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.

* Corresponding author. Mailing address: Departments of Adult Oncology, Medicine and Genetics, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney St., Boston, MA 02115. Phone: (617) 632-6085. Fax: (617) 632-6069. E-mail: ron_depinho{at}dfci.harvard.edu.

{dagger} Present address: Schering-Plough Research Institute, Kenilworth, NJ 07033.

Molecular and Cellular Biology, April 2002, p. 2743-2750, Vol. 22, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.8.2743-2750.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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