卫星 DNA 阵列对 7 号染色体进行编码，并通过 ZFP819 调节全能性。
A satellite DNA array barcodes chromosome 7 and regulates totipotency via ZFP819.
机构信息
Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London E1 2AT, UK.
Bill Lyons Informatics Centre, UCL Cancer Institute, London WC1E 6BT, UK.
出版信息
Sci Adv. 2022 Oct 28;8(43):eabp8085. doi: 10.1126/sciadv.abp8085.
Mammalian genomes are a battleground for genetic conflict between repetitive elements and KRAB-zinc finger proteins (KZFPs). We asked whether KZFPs can regulate cell fate by using ZFP819, which targets a satellite DNA array, ZP3AR. ZP3AR coats megabase regions of chromosome 7 encompassing genes encoding ZSCAN4, a master transcription factor of totipotency. Depleting ZFP819 in mouse embryonic stem cells (mESCs) causes them to transition to a 2-cell (2C)-like state, whereby the ZP3AR array switches from a poised to an active enhancer state. This is accompanied by a global erosion of heterochromatin roadblocks, which we link to decreased SETDB1 stability. These events result in transcription of active LINE-1 elements and impaired differentiation. In summary, ZFP819 and TRIM28 partner up to close chromatin across , to promote exit from totipotency. We propose that satellite DNAs may control developmental fate transitions by barcoding and switching off master transcription factor genes.
哺乳动物基因组是重复元件和 KRAB 锌指蛋白（KZFPs）之间遗传冲突的战场。我们通过靶向卫星 DNA 阵列 ZP3AR 的 ZFP819 来询问 KZFPs 是否可以通过调节细胞命运。ZP3AR 覆盖了染色体 7 的大片段区域，包含编码全能性主转录因子 ZSCAN4 的基因。在小鼠胚胎干细胞（mESCs）中耗尽 ZFP819 会导致它们向 2 细胞（2C）样状态转变，其中 ZP3AR 阵列从静止状态转变为活跃的增强子状态。这伴随着异染色质路障的全面侵蚀，我们将其与 SETDB1 稳定性降低联系起来。这些事件导致活跃的 LINE-1 元件转录和分化受损。总之，ZFP819 和 TRIM28 合作来关闭染色质，以促进全能性的退出。我们提出，卫星 DNA 可能通过编码和关闭主转录因子基因来控制发育命运的转变。
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