H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction
H1 linker histones silence repetitive elements by promoting both histone H3K9 methylation and chromatin compaction
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DOI：
10.1073/pnas.1920725117
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发表时间：
2020-06-23
影响因子：
11.1
通讯作者：
Skoultchi, Arthur I.
中科院分区：
文献类型：
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作者：
Healton, Sean E.;Pinto, Hugo D.;Skoultchi, Arthur I.
近50%的小鼠和人类基因组是由重复序列组成的。这些序列的转录在发育过程中受到严格控制，以防止基因组不稳定、不适当的基因激活和其他不适应过程。在这里，我们证明了H1连接体组蛋白在小鼠胚胎干细胞中沉默重复元件的整体作用。强烈的H1缺失导致多种重复序列的深度去抑制，包括主要的卫星序列、LINE -1和ERV。重复序列转录的激活伴随着重复序列染色质H3K9三甲基化的降低。H1连接体组蛋白直接与Suv39h1、Suv39h2和SETDB1相互作用，这些组蛋白甲基转移酶在这些区域内负责染色质的H3K9三甲基化，并在体外刺激它们对染色质的活性。然而，我们也暗示由H1介导的染色质压缩是重复主要卫星序列沉默的一个额外的、主要的抑制机制。我们的研究结果阐明了两种不同的H1介导的异染色质沉默途径。
Nearly 50% of mouse and human genomes are composed of repetitive sequences. Transcription of these sequences is tightly controlled during development to prevent genomic instability, inappropriate gene activation and other maladaptive processes. Here, we demonstrate an integral role for H1 linker histones in silencing repetitive elements in mouse embryonic stem cells. Strong H1 depletion causes a profound de -repression of several classes of repetitive sequences, including major satellite, LINE -1, and ERV. Activation of repetitive sequence transcrip- tion is accompanied by decreased H3K9 trimethylation of repetitive sequence chromatin. H1 linker histones interact directly with Suv39h1, Suv39h2, and SETDB1, the histone methyltransferases responsible for H3K9 trimethylation of chromatin within these regions, and stimulate their activity toward chromatin in vitro. However, we also implicate chromatin compaction mediated by H1 as an additional, dominant re- pressive mechanism for silencing of repetitive major satellite se- quences. Our findings elucidate two distinct, H1 -mediated pathways for silencing heterochromatin.