Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency
| Autor: | Aliaksandra Radzisheuskaya, Vincent Pasque, Maryna Panamarova, Richard P. Halley-Stott, Magdalena Zernicka-Goetz, Astrid Gillich, José C. R. Silva, M. Azim Surani |
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| Rok vydání: | 2012 |
| Předmět: |
Epigenomics
Male Pluripotent Stem Cells Cellular differentiation Rex1 Embryoid body Biology Transfection Histones Mice 03 medical and health sciences 0302 clinical medicine Nuclear reprogramming Animals Induced pluripotent stem cell Cell potency Embryonic Stem Cells 030304 developmental biology 0303 health sciences Induced stem cells Induced pluripotency Cell commitment macroH2A Gene Expression Regulation Developmental Cell Differentiation Cell Biology Cellular Reprogramming Molecular biology Embryonic stem cell Cell biology Mice Inbred C57BL 030220 oncology & carcinogenesis Epigenetic stability Mice Inbred CBA Female Stem cell Research Article |
| Zdroj: | Journal of Cell Science |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.113019 |
| Popis: | How cell fate becomes restricted during somatic cell differentiation is a long-lasting question in biology. Epigenetic mechanisms not present in pluripotent cells and acquired during embryonic development are expected to stabilize the differentiated state of somatic cells and thereby restrict their ability to convert to another fate. The histone variant macroH2A acts as a component of an epigenetic multilayer that heritably maintains the silent X chromosome and has been shown to restrict tumor development. Here we show that macroH2A marks the differentiated cell state during mouse embryogenesis. MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development. Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells. Removal of macroH2A.1, macroH2A.2 or both increased the efficiency of induced pluripotency up to 25-fold. The obtained induced pluripotent stem cells reactivated pluripotency genes, silenced retroviral transgenes and contributed to chimeras. In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. In summary, our study identifies for the first time a link between an epigenetic mark and cell fate restriction during somatic cell differentiation, which helps to maintain cell identity and antagonizes induction of a pluripotent stem cell state. ispartof: JOURNAL OF CELL SCIENCE vol:125 issue:24 pages:6094-6104 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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