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A System for Genome-Wide Histone Variant Dynamics in ES Cells Reveals Dynamic MacroH2A2 Replacement at Promoters
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نویسنده
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yildirim o. ,hung j.-h. ,cedeno r.j. ,weng z. ,lengner c.j. ,rando o.j.
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منبع
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plos genetics - 2014 - دوره : 10 - شماره : 8
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چکیده
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Dynamic exchange of a subset of nucleosomes in vivo plays important roles in epigenetic inheritance of chromatin states,chromatin insulator function,chromosome folding,and the maintenance of the pluripotent state of embryonic stem cells. here,we extend a pulse-chase strategy for carrying out genome-wide measurements of histone dynamics to several histone variants in murine embryonic stem cells and somatic tissues,recapitulating expected characteristics of the well characterized h3.3 histone variant. we extended this system to the less-studied macroh2a2 variant,commonly described as a “repressive” histone variant whose accumulation in chromatin is thought to fix the epigenetic state of differentiated cells. unexpectedly,we found that while large intergenic blocks of macroh2a2 were stably associated with the genome,promoter-associated peaks of macroh2a2 exhibited relatively rapid exchange dynamics in es cells,particularly at highly-transcribed genes. upon differentiation to embryonic fibroblasts,macroh2a2 was gained primarily in additional long,stably associated blocks across gene-poor regions,while overall turnover at promoters was greatly dampened. our results reveal unanticipated dynamic behavior of the macroh2a2 variant in pluripotent cells,and provide a resource for future studies of tissue-specific histone dynamics in vivo. © 2014 yildirim et al.
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آدرس
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department of biochemistry and molecular pharmacology,university of massachusetts medical school,worcester,ma,united states,department of molecular biology,massachusetts general hospital,department of genetics,harvard medical school,boston,ma, United States, integrative biology,university of massachusetts medical school,worcester,ma,united states,department of biological science and technology and institute of bioinformatics and systems biology,national chao-tung university, Taiwan, department of animal biology,school of veterinary medicine and institute for regenerative medicine,university of pennsylvania,philadelphia,pa, United States, department of biochemistry and molecular pharmacology,university of massachusetts medical school,worcester,ma,united states,integrative biology,university of massachusetts medical school,worcester,ma, United States, department of animal biology,school of veterinary medicine and institute for regenerative medicine,university of pennsylvania,philadelphia,pa, United States, department of biochemistry and molecular pharmacology,university of massachusetts medical school,worcester,ma, United States
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Authors
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