BAF 复合物介导的染色质弛豫对于建立 X 染色体失活是必需的。
BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation.
机构信息
The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
The Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia.
出版信息
Nat Commun. 2022 Mar 29;13(1):1658. doi: 10.1038/s41467-022-29333-1.
The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly.
表观遗传沉默的过程虽然至关重要，但尚未被完全理解。在这里，我们报告了一个可再生的雌性小鼠胚胎干细胞（mESC）系统 Xmas，它可以快速评估 X 染色体失活（XCI），这是雌性哺乳动物中两个 X 染色体之一的表观遗传沉默机制，可实现剂量补偿。通过在分化的 Xmas mESCs 中进行靶向遗传筛选，我们揭示了 BAF 复合物在 XCI 建立的最早阶段，需要在失活 X 染色体上的启动子处创建无核小体区域。如果没有这种作用，基因沉默就会失败。Xmas mESCs 为基于筛选的方法提供了一个易于处理的模型，这些方法可以发现 XCI 和更广泛的表观遗传沉默的女性特有的未知方面。
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