A Method for Genetically Installing Site-Specific Acetylation in Recombinant Histories Defines the Effects of H3 K56 Acetylation

被引：386

作者：

Neumann, Heinz ^{[1
]}

Hancock, Susan M. ^{[1
]}

Buning, Ruth ^{[2
]}

Routh, Andrew ^{[1
]}

Chapman, Lynda ^{[1
]}

Somers, Joanna ^{[3
]}

Owen-Hughes, Tom ^{[3
]}

van Noort, John ^{[2
]}

Rhodes, Daniela ^{[1
]}

Chin, Jason W. ^{[1
]}

机构：

[1] MRC, Mol Biol Lab, Cambridge CB2 0QH, England

[2] Leiden Univ, Leiden Inst Phys, NL-2300 RA Leiden, Netherlands

[3] Univ Dundee, Sch Life Sci, Wellcome Trust Ctr Gene Regulat & Express, Dundee DD1 5EH, Scotland

来源：

MOLECULAR CELL | 2009年 / 36卷 / 01期

基金：

英国惠康基金; 欧洲研究理事会; 英国医学研究理事会;

关键词：

NUCLEOSOME CORE PARTICLE; NM CHROMATIN FIBER; HISTONE H3; H4-K16; ACETYLATION; PHD FINGER; LYSINE; 56; BINDING; METHYLATION; BROMODOMAIN; EXCHANGE;

D O I：

10.1016/j.molcel.2009.07.027

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：

Lysine acetylation of histones defines the epigenetic status of human embryonic stem cells and orchestrates DNA replication, chromosome condensation, transcription, telomeric silencing, and DNA repair. A detailed mechanistic explanation of these phenomena is impeded by the limited availability of homogeneously acetylated histones. We report a general method for the production of homogeneously and site-specifically acetylated recombinant histones by genetically encoding acetyl-lysine. We reconstitute histone octamers, nucleosomes, and nucleosomal arrays bearing defined acetylated lysine residues. With these designer nucleosomes, we demonstrate that, in contrast to the prevailing dogma, acetylation of H3 K56 does not directly affect the compaction of chromatin and has modest effects on remodeling by SWI/SNF and RSC. Single-molecule FRET experiments reveal that H3 K56 acetylation increases DNA breathing 7-fold. Our results provide a molecular and mechanistic underpinning for cellular phenomena that have been linked with K56 acetylation.

引用

页码：153 / 163

页数：11

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