Identification of mammalian Sds3 as an integral component of the Sin3/histone deacetylase corepressor complex.
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.
Alland
Leila
L
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
David
Gregory
G
Shen-Li
Hong
H
Potes
Jason
J
Muhle
Rebecca
R
Lee
Hye-Chun
HC
Hou
Harry
H
Chen
Ken
K
DePinho
Ronald A
RA
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D002265:Carboxylic Ester Hydrolases; C430718:SDS3 protein, S cerevisiae; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex