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准确的 H3K27 甲基化可以由 SUZ12 定向的 PRC2 从头建立。

Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2.

机构信息

Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Nat Struct Mol Biol. 2018 Mar;25(3):225-232. doi: 10.1038/s41594-018-0036-6. Epub 2018 Feb 26.

DOI:10.1038/s41594-018-0036-6
PMID:29483650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5842896/
Abstract

Polycomb repressive complex 2 (PRC2) catalyzes methylation on lysine 27 of histone H3 (H3K27) and is required for maintaining transcriptional patterns and cellular identity, but the specification and maintenance of genomic PRC2 binding and H3K27 methylation patterns remain incompletely understood. Epigenetic mechanisms have been proposed, wherein pre-existing H3K27 methylation directs recruitment and regulates the catalytic activity of PRC2 to support its own maintenance. Here we investigate whether such mechanisms are required for specifying H3K27 methylation patterns in mouse embryonic stem cells (mESCs). Through re-expression of PRC2 subunits in PRC2-knockout cells that have lost all H3K27 methylation, we demonstrate that methylation patterns can be accurately established de novo. We find that regional methylation kinetics correlate with original methylation patterns even in their absence, and specification of the genomic PRC2 binding pattern is retained and specifically dependent on the PRC2 core subunit SUZ12. Thus, the H3K27 methylation patterns in mESCs are not dependent on self-autonomous epigenetic inheritance.

摘要

多梳抑制复合物 2 (PRC2) 催化组蛋白 H3 赖氨酸 27 位的甲基化 (H3K27)，对于维持转录模式和细胞身份是必需的，但基因组 PRC2 结合和 H3K27 甲基化模式的特异性和维持仍不完全清楚。已经提出了表观遗传机制，其中预先存在的 H3K27 甲基化指导 PRC2 的募集和调节其自身维持的催化活性。在这里，我们研究了这些机制是否需要在小鼠胚胎干细胞 (mESC) 中指定 H3K27 甲基化模式。通过在已经失去所有 H3K27 甲基化的 PRC2 敲除细胞中重新表达 PRC2 亚基，我们证明可以从头准确地建立甲基化模式。我们发现，即使没有区域甲基化动力学与原始甲基化模式相关，基因组 PRC2 结合模式的特异性仍然保留，并特异性地依赖于 PRC2 核心亚基 SUZ12。因此，mESC 中的 H3K27 甲基化模式不依赖于自我自主的表观遗传遗传。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/4b7325ba1d85/emss-75815-f006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/4b7325ba1d85/emss-75815-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/0cabcc1501d7/emss-75815-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/ded7f5dd7ff6/emss-75815-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/ff0116d8641c/emss-75815-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/b6a8c9401c5a/emss-75815-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/2c216ed9a68e/emss-75815-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3824/5842896/4b7325ba1d85/emss-75815-f006.jpg

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