Histione H2A monoubiquitination represses transcription by inhibiting RNA polymerase II transcriptional elongation

被引：294

作者：

Zhou, Wenlai ^{[1
,2
]}

Zhu, Ping ^{[1
,2
]}

Wang, Jianxun ^{[1
,2
]}

Pascual, Gabriel ^{[3
]}

Ohgi, Kenneth A. ^{[1
,2
]}

Lozach, Jean ^{[3
]}

Glass, Christopher K. ^{[3
]}

Rosenfeld, Michael G. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

来源：

MOLECULAR CELL | 2008年 / 29卷 / 01期

关键词：

D O I：

10.1016/j.molcel.2007.11.002

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：

Solving the biological roles of covalent histone modifications, including monoubiquitination of histone H2A, and the molecular mechanisms by which these modifications regulate specific transcriptional programs remains a central question for all eukaryotes. Here we report that the N-CoR/HDAC1/3 complex specifically recruits a specific histone H2A ubiquitin ligase, 2A-HUB/hRUL138, to a subset of regulated gene promoters. 2A-HUB catalyzes monoubiquitination of H2A at lysine 119, functioning as a combinatoric component of the repression machinery required for specific gene regulation programs. Thus, 2A-HUB mediates a selective repression of a specific set of chemokine genes in macrophages, critically modulating migratory responses to TLR activation. H2A monoubiquitination acts to prevent FACT recruitment at the transcriptional promoter region, blocking RNA polymerase 11 release at the early stage of elongation. We suggest that distinct H2A ubiquitinases, each recruited based on interactions with different corepressor complexes, contribute to distinct transcriptional repression programs.

引用

页码：69 / 80

页数：12

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