Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. In our current understanding, nucleosome turnover is universally linked to DNA accessibility and histone acetylation. In mouse embryonic stem cells, H3.3 is also highly enriched at interstitial heterochromatin, most prominently intracisternal-A particle endogenous retroviral elements. Interstitial heterochromatin is established over confined domains by the TRIM28/SETDB1 corepressor complex and has stereotypical features of repressive chromatin, such as H3K9me3 and recruitment of all HP1 isoforms. Making use of available genome-wide datasets, we demonstrate that fast histone turnover and H3.3 incorporation is compatible with these hallmarks of heterochromatin. Further, we find that histone H3.3 is required to maintain minimal DNA accessibility in this surprisingly dynamic heterochromatin state. Loss of H3.3 in mouse embryonic stem cells elicits a highly specific opening of interstitial heterochromatin with minimal effects on other silent or active regions of the genome.

中文翻译：

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胚胎干细胞特异的异染色质状态可以在没有DNA可及性的情况下交换核心组蛋白

与不依赖复制的组蛋白变体H3.3结合的核小体更新是动物基因组调控区的标志。根据我们目前的理解，核小体的更新通常与DNA的可及性和组蛋白乙酰化有关。在小鼠胚胎干细胞中，H3.3在间质异染色质中也高度富集，最显着的是脑池内A颗粒内源性逆转录病毒元件。间质异染色质是由TRIM28 / SETDB1核心表达复合物在限定域上建立的，具有抑制染色质的定型特征，例如H3K9me3和所有HP1亚型的募集。利用可用的全基因组数据集，我们证明了快速的组蛋白更新和H3.3掺入与异染色质的这些特征兼容。进一步，我们发现，在这种令人惊讶的动态异染色质状态下，需要组蛋白H3.3才能保持最小的DNA可及性。小鼠胚胎干细胞中H3.3的丢失会引起间质异染色质的高度特异性开放，而对基因组的其他沉默或活跃区域的影响却很小。