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Contribution of epigenetic landscapes and transcription factors to X-chromosome reactivation in the inner cell mass

Maud Borensztein, Ikuhiro Okamoto, Laurène Syx, Guillaume Guilbaud, Christel Picard, Katia Ancelin, Rafael Galupa, Patricia Diabangouaya, Nicolas Servant, Emmanuel Barillot, Azim Surani, Mitinori Saitou, Chong-Jian Chen, Konstantinos Anastassiadis and Edith Heard ()
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Maud Borensztein: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Ikuhiro Okamoto: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Laurène Syx: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Guillaume Guilbaud: Medical Research Council Laboratory of Molecular Biology
Christel Picard: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Katia Ancelin: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Rafael Galupa: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Patricia Diabangouaya: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne
Nicolas Servant: PSL Research University, Mines Paris Tech, INSERM U900
Emmanuel Barillot: PSL Research University, Mines Paris Tech, INSERM U900
Azim Surani: University of Cambridge
Mitinori Saitou: Kyoto University
Chong-Jian Chen: Annoroad Gene Technology Co., Ltd
Konstantinos Anastassiadis: Technische Universität Dresden
Edith Heard: PSL Research University, CNRS UMR3215, INSERM U934, UPMC Paris-Sorbonne

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract X-chromosome inactivation is established during early development. In mice, transcriptional repression of the paternal X-chromosome (Xp) and enrichment in epigenetic marks such as H3K27me3 is achieved by the early blastocyst stage. X-chromosome inactivation is then reversed in the inner cell mass. The mechanisms underlying Xp reactivation remain enigmatic. Using in vivo single-cell approaches (allele-specific RNAseq, nascent RNA-fluorescent in situ hybridization and immunofluorescence), we show here that different genes are reactivated at different stages, with more slowly reactivated genes tending to be enriched in H3meK27. We further show that in UTX H3K27 histone demethylase mutant embryos, these genes are even more slowly reactivated, suggesting that these genes carry an epigenetic memory that may be actively lost. On the other hand, expression of rapidly reactivated genes may be driven by transcription factors. Thus, some X-linked genes have minimal epigenetic memory in the inner cell mass, whereas others may require active erasure of chromatin marks.

Date: 2017
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DOI: 10.1038/s41467-017-01415-5

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