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Mol Cell. 2016 Sep 15;63(6):1066-79. doi: 10.1016/j.molcel.2016.08.032.

Resetting Epigenetic Memory by Reprogramming of Histone Modifications in Mammals.

Author information

1
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
2
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; PKU-THU Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
3
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A(∗)STAR), Singapore 117609, Singapore.
4
Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A(∗)STAR), Singapore 117609, Singapore; Institute of Molecular and Cell Biology, A(∗)STAR, Singapore 138673, Singapore.
5
Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: xiewei121@tsinghua.edu.cn.

Abstract

Polycomb group proteins and the related histone modification H3K27me3 can maintain the silencing of key developmental regulators and provide cellular memory. However, how such an epigenetic state is reprogrammed and inherited between generations is poorly understood. Using an ultra-sensitive approach, STAR ChIP-seq, we investigated H3K27me3 across 14 developmental stages along mouse gametogenesis and early development. Interestingly, highly pervasive H3K27me3 is found in regions depleted of transcription and DNA methylation in oocytes. Unexpectedly, we observed extensive loss of promoter H3K27me3 at Hox and other developmental genes upon fertilization. This is accompanied by global erasure of sperm H3K27me3 but inheritance of distal H3K27me3 from oocytes. The resulting allele-specific H3K27me3 patterns persist to blastocysts before being converted to canonical forms in postimplantation embryos, where both H3K4me3/H3K27me3 bivalent promoter marks are restored at developmental genes. Together, these data revealed widespread resetting of epigenetic memory and striking plasticity of epigenome during gametogenesis and early development.

PMID:
27635762
DOI:
10.1016/j.molcel.2016.08.032
[Indexed for MEDLINE]
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