Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection.
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.
Nicolas
Estelle
E
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, US National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.
Yamada
Takatomi
T
Cam
Hugh P
HP
Fitzgerald
Peter C
PC
Kobayashi
Ryuji
R
Grewal
Shiv I S
SI
D018797:Cell Cycle Proteins; D002843:Chromatin / Q000235:genetics; D004249:DNA Damage; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000502:physiology; D016372:RNA, Antisense; D012333:RNA, Messenger; D012568:Schizosaccharomyces / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D014158:Transcription, Genetic
D018797:Cell Cycle Proteins; D002843:Chromatin; C115303:Clr6 protein, S pombe; D046912:Multiprotein Complexes; D016372:RNA, Antisense; D012333:RNA, Messenger; D029702:Schizosaccharomyces pombe Proteins; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex