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PcG 复合物在复制前的早期 S 期为基因沉默的表观遗传遗传奠定了基础。

PcG complexes set the stage for epigenetic inheritance of gene silencing in early S phase before replication.

机构信息

Epigenetics and Genome Reprogramming, Dulbecco Telethon Institute, IRCCS Santa Lucia Foundation, Rome, Italy.

出版信息

PLoS Genet. 2011 Nov;7(11):e1002370. doi: 10.1371/journal.pgen.1002370. Epub 2011 Nov 3.

DOI:10.1371/journal.pgen.1002370
PMID:22072989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3207895/
Abstract

Polycomb group (PcG) proteins are part of a conserved cell memory system that conveys epigenetic inheritance of silenced transcriptional states through cell division. Despite the considerable amount of information about PcG mechanisms controlling gene silencing, how PcG proteins maintain repressive chromatin during epigenome duplication is still unclear. Here we identified a specific time window, the early S phase, in which PcG proteins are recruited at BX-C PRE target sites in concomitance with H3K27me3 repressive mark deposition. Notably, these events precede and are uncoupled from PRE replication timing, which occurs in late S phase when most epigenetic signatures are reduced. These findings shed light on one of the key mechanisms for PcG-mediated epigenetic inheritance during S phase, suggesting a conserved model in which the PcG-dependent H3K27me3 mark is inherited by dilution and not by de novo methylation occurring at the time of replication.

摘要

多梳抑制复合物(PcG)蛋白是细胞记忆系统的一部分,通过细胞分裂将沉默转录状态的表观遗传传递下去。尽管已经有大量关于 PcG 机制控制基因沉默的信息,但 PcG 蛋白如何在表观基因组复制过程中维持抑制性染色质仍然不清楚。在这里,我们确定了一个特定的时间窗口,即早期 S 期,在此期间 PcG 蛋白与 H3K27me3 抑制性标记沉积一起被募集到 BX-C PRE 靶位点。值得注意的是,这些事件发生在 PRE 复制时间之前,并且与 PRE 复制时间解耦,PRE 复制时间发生在晚期 S 期,此时大多数表观遗传特征减少。这些发现揭示了 PcG 介导的 S 期表观遗传传递的关键机制之一,表明了一个保守的模型,其中 PcG 依赖性的 H3K27me3 标记通过稀释而不是在复制时发生的从头甲基化来传递。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/64042e11ee09/pgen.1002370.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/98036ced73fa/pgen.1002370.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/7767dcf0ef50/pgen.1002370.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/f36f6f7a902f/pgen.1002370.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/dfeaa67b13fa/pgen.1002370.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/64042e11ee09/pgen.1002370.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/98036ced73fa/pgen.1002370.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/7767dcf0ef50/pgen.1002370.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/f36f6f7a902f/pgen.1002370.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/dfeaa67b13fa/pgen.1002370.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c9b/3207895/64042e11ee09/pgen.1002370.g005.jpg

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