A system for genome-wide histone variant dynamics in ES cells reveals dynamic MacroH2A2 replacement at promoters
Cedeno, Ryan J.
Lengner, Christopher J.
Rando, Oliver J.
UMass Chan AffiliationsProgram in Bioinformatics and Integrative Biology
Department of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
KeywordsCell and Developmental Biology
Genetics and Genomics
MetadataShow full item record
AbstractDynamic 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.
SourcePLoS Genet. 2014 Aug 7;10(8):e1004515. doi: 10.1371/journal.pgen.1004515. eCollection 2014. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39668
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.
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>