Wirén Marianna, Silverstein Rebecca A, Sinha Indranil, Walfridsson Julian, Lee Hang-Mao, Laurenson Patricia, Pillus Lorraine, Robyr Daniel, Grunstein Michael, Ekwall Karl
Karolinska Institutet, Department of Biosciences/School of Life Sciences, University College Sodertorn, Huddinge, Sweden.
EMBO J. 2005 Aug 17;24(16):2906-18. doi: 10.1038/sj.emboj.7600758. Epub 2005 Aug 4.
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.
我们对裂殖酵母（粟酒裂殖酵母）中代表三种不同系统发育类别的四种组蛋白脱乙酰基酶（HDAC）的酶特异性、表达谱和结合位点进行了全基因组研究。通过直接比较基因间区域和编码区域中的核小体密度、组蛋白乙酰化模式以及HDAC结合与基因表达谱，我们发现Sir2（III类）和Hos2（I类）在防止组蛋白丢失方面发挥作用；Clr6（I类）是启动子定位抑制中的主要酶。Hos2通过使其开放阅读框中的H4K16Ac去乙酰化，在促进生长相关基因的高表达中发挥了意想不到的作用。Clr3（II类）在整个基因组中，包括沉默区域：核糖体DNA、着丝粒、mat2/3和端粒，与Sir2协同作用。在其基因组靶点上，Clr3最显著的乙酰化位点是H3K14Ac，Sir2是H3K9Ac。Clr3还影响包含成簇的应激和减数分裂诱导基因的亚端粒区域。因此，这种综合的基因组方法揭示了裂殖酵母HDAC在沉默区域对基因表达的抑制和激活中发挥的不同作用。
