Genome-wide function of H2B ubiquitylation in promoter and genic regions
Genome-wide function of H2B ubiquitylation in promoter and genic regions
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DOI：
10.1101/gad.177238.111
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发表时间：
2011-11-01
影响因子：
10.5
通讯作者：
Pugh, B. Franklin
中科院分区：
文献类型：
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作者：
Batta, Kiran;Zhang, Zhenhai;Pugh, B. Franklin
基因内部和周围的核小体组织可能对转录调控有实质性的贡献。组蛋白修饰对全基因组核小体组织的贡献尚未得到系统评价。在本研究中，我们研究了H2 BK 123泛素化的作用，几个组蛋白修饰的关键调节剂，在启动子，基因和转录终止区域的酿酒酵母核小体组织。使用高分辨率MNase染色质免疫沉淀和测序（ChIP-seq），我们绘制了H2 BK 123泛素化途径突变体的核小体定位和占用。我们发现，H2 B泛素化介导的核小体的形成和/或稳定性抑制组装的转录机器在正常静止的启动子，而高度活跃的基因体内的泛素化促进转录延伸。这种调节不通过H3 K4、K36和K79处的泛素化调节的组蛋白标记进行。我们的研究结果表明，H2 B泛素化（核小体组装）的机制相似的功能引起不同的功能结果的基因取决于其位置的启动子（抑制）与转录区域（激活）。
Nucleosomal organization in and around genes may contribute substantially to transcriptional regulation. The contribution of histone modifications to genome-wide nucleosomal organization has not been systematically evaluated. In the present study, we examine the role of H2BK123 ubiquitylation, a key regulator of several histone modifications, on nucleosomal organization at promoter, genic, and transcription termination regions in Saccharomyces cerevisiae. Using high-resolution MNase chromatin immunoprecipitation and sequencing (ChIP-seq), we map nucleosome positioning and occupancy in mutants of the H2BK123 ubiquitylation pathway. We found that H2B ubiquitylation-mediated nucleosome formation and/or stability inhibits the assembly of the transcription machinery at normally quiescent promoters, whereas ubiquitylation within highly active gene bodies promotes transcription elongation. This regulation does not proceed through ubiquitylation-regulated histone marks at H3K4, K36, and K79. Our findings suggest that mechanistically similar functions of H2B ubiquitylation (nucleosome assembly) elicit different functional outcomes on genes depending on its positional context in promoters (repressive) versus transcribed regions (activating).