Propagation of Polycomb-repressed chromatin requires sequence-specific recruitment to DNA
Propagation of Polycomb-repressed chromatin requires sequence-specific recruitment to DNA
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DOI：
10.1126/science.aai8266
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发表时间：
2017-04-07
期刊：
影响因子：
56.9
通讯作者：
Mueller, Juerg
中科院分区：
文献类型：
--
作者：
Laprell, Friederike;Finkl, Katja;Mueller, Juerg
表观遗传模型表明，在Polycomb阻遏过程中，Polycomb阻遏复合物2（PRC2）不依赖于DNA序列而增殖组蛋白H3赖氨酸27三甲基化（H3K27me3）。我们表明，插入Polycomb响应元件（PRE）DNA到果蝇基因组中创建扩展域的H3K27me3修饰的核小体在侧翼染色质，并导致一个链接的报告基因的镇压。切除PRE DNA后，H3K27me3核小体随着每轮DNA复制而稀释，报告基因阻遏消失。在复制停滞的细胞中切除后，H3K27me3水平保持高水平，抑制持续存在。因此，H3K27me3标记的核小体提供了一种在复制过程中以不依赖于序列的方式传递给子链DNA的抑制记忆。相反，H3K27三甲基化向新掺入的核小体的传播需要PRC2向PRE DNA的序列特异性靶向。
Epigenetic inheritance models posit that during Polycomb repression, Polycomb repressive complex 2 (PRC2) propagates histone H3 lysine 27 trimethylation (H3K27me3) independently of DNA sequence. We show that insertion of Polycomb response element (PRE) DNA into the Drosophila genome creates extended domains of H3K27me3-modified nucleosomes in the flanking chromatin and causes repression of a linked reporter gene. After excision of PRE DNA, H3K27me3 nucleosomes become diluted with each round of DNA replication, and reporter gene repression is lost. After excision in replication-stalled cells, H3K27me3 levels stay high and repression persists. H3K27me3-marked nucleosomes therefore provide amemory of repression that is transmitted in a sequence-independent manner to daughter strand DNA during replication. In contrast, propagation of H3K27 trimethylation to newly incorporated nucleosomes requires sequence-specific targeting of PRC2 to PRE DNA.