Article abstract
Nature Structural & Molecular Biology 14, 372 - 380 (2007)
Published online: 22 April 2007 | doi:10.1038/nsmb1239
Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection
Estelle Nicolas1, Takatomi Yamada1,4, Hugh P Cam1, Peter C FitzGerald2, Ryuji Kobayashi3 & Shiv I S Grewal1
Abstract
Histone acetylation is important in regulating DNA accessibility. Multifunctional Sin3 proteins bind histone deacetylases (HDACs) to assemble silencing complexes that selectively target chromatin. We show that, in fission yeast, an essential HDAC, Clr6, exists in two distinct Sin3 core complexes. Complex I contains an essential Sin3 homolog, Pst1, and other factors, and predominantly targets gene promoters. Complex II contains a nonessential Sin3 homolog, Pst2, and several conserved proteins. It preferentially targets transcribed chromosomal regions and centromere cores. Defects in complex II abrogate global protective functions of chromatin, causing increased accessibility of DNA to genotoxic agents and widespread antisense transcripts that are processed by the exosome. Notably, the two Clr6 complexes differentially repress forward and reverse centromeric repeat transcripts, suggesting that these complexes regulate transcription in heterochromatin and euchromatin in similar manners, including suppression of spurious transcripts from cryptic start sites.
- Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
- Genome Analysis Unit, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
- Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
- Present address: Genetic System Regulation Laboratory, RIKEN, Wako, Saitama, Japan.
Correspondence to: Shiv I S Grewal1 e-mail: grewals@mail.nih.gov
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