Genome wide analysis of nucleosome density histone acetylation and HDAC function in fission yeast

被引:124
作者
Wirén, M
Silverstein, RA
Sinha, I
Walfridsson, J
Lee, HM
Laurenson, P
Pillus, L
Robyr, D
Grunstein, M
Ekwall, K
机构
[1] Univ Coll Sodertorn, Karolinska Inst, Sch Life Sci, Dept Biosci, S-14189 Huddinge, Sweden
[2] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA
[4] Univ Calif Los Angeles, Dept Biol Chem, Sch Med, Los Angeles, CA 90024 USA
[5] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA
关键词
chromatin; fission yeast; gene regulation genomewide; HDAC;
D O I
10.1038/sj.emboj.7600758
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have conducted a genomewide investigation into the enzymatic specificity, expression profiles, and binding locations of four histone deacetylases (HDACs), representing the three different phylogenetic classes in fission yeast ( Schizosaccharomyces pombe). By directly comparing nucleosome density, histone acetylation patterns and HDAC binding in both intergenic and coding regions with gene expression profiles, we found that Sir2 ( class III) and Hos2 ( class I) have a role in preventing histone loss; Clr6 ( class I) is the principal enzyme in promoter-localized repression. Hos2 has an unexpected role in promoting high expression of growth-related genes by deacetylating H4K16Ac in their open reading frames. Clr3 ( class II) acts cooperatively with Sir2 throughout the genome, including the silent regions: rDNA, centromeres, mat2/3 and telomeres. The most significant acetylation sites are H3K14Ac for Clr3 and H3K9Ac for Sir2 at their genomic targets. Clr3 also affects subtelomeric regions which contain clustered stress- and meiosis-induced genes. Thus, this combined genomic approach has uncovered different roles for fission yeast HDACs at the silent regions in repression and activation of gene expression.
引用
收藏
页码:2906 / 2918
页数:13
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