A system for genome-wide histone variant dynamics in ES cells reveals dynamic MacroH2A2 replacement at promoters
Authors
Yildirim, OzlemHung, Jui-Hung
Cedeno, Ryan J.
Weng, Zhiping
Lengner, Christopher J.
Rando, Oliver J.
UMass Chan Affiliations
Program in Bioinformatics and Integrative BiologyDepartment of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2014-08-07Keywords
Cell and Developmental BiologyCell Biology
Cells
Computational Biology
Genetics
Genetics and Genomics
Genomics
Metadata
Show full item recordAbstract
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.Source
PLoS Genet. 2014 Aug 7;10(8):e1004515. doi: 10.1371/journal.pgen.1004515. eCollection 2014. Link to article on publisher's siteDOI
10.1371/journal.pgen.1004515Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39668PubMed ID
25102063Notes
First author Ozlem Yildirim is a doctoral student in the Interdisciplinary Graduate Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1371/journal.pgen.1004515
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Except where otherwise noted, this item's license is described as <p>This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>