Global Regulation of H2A.Z Localization by the INO80 Chromatin-Remodeling Enzyme Is Essential for Genome Integrity

被引：321

作者：

Papamichos-Chronakis, Manolis ^{[1
]}

Watanabe, Shinya ^{[1
]}

Rando, Oliver J. ^{[2
]}

Peterson, Craig L. ^{[1
]}

机构：

[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA

[2] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01655 USA

来源：

CELL | 2011年 / 144卷 / 02期

基金：

美国国家卫生研究院;

关键词：

HISTONE VARIANT H2A.Z; SACCHAROMYCES-CEREVISIAE; DNA-REPLICATION; RECOMBINANT HISTONES; CELL-CYCLE; COMPLEX; ACETYLATION; REPAIR; YEAST; TRANSCRIPTION;

D O I：

10.1016/j.cell.2010.12.021

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：

INO80 is an evolutionarily conserved, ATP-dependent chromatin-remodeling enzyme that plays roles in transcription, DNA repair, and replication. Here, we show that yeast INO80 facilitates these diverse processes at least in part by controlling genome-wide distribution of the histone variant H2A.Z. In the absence of INO80, H2A.Z nucleosomes are mislocalized, and H2A.Z levels at promoters show reduced responsiveness to transcriptional changes, suggesting that INO80 controls H2A.Z dynamics. Additionally, we demonstrate that INO80 has a histone-exchange activity in which the enzyme can replace nucleosomal H2A.Z/H2B with free H2A/H2B dimers. Genetic interactions between ino80 and htz1 support a model in which INO80 catalyzes the removal of unacetylated H2A.Z from chromatin as a mechanism to promote genome stability.

引用

页码：200 / 213

页数：14

共 38 条

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[33] Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability
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[34] The Schizosaccharomyces pombe JmjC-Protein, Msc1, Prevents H2A.Z Localization in Centromeric and Subtelomeric Chromatin Domains
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[37] Analysis of active chromatin modifications in early mammalian embryos reveals uncoupling of H2A.Z acetylation and H3K36 trimethylation from embryonic genome activation
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