生物
异染色质
构成性异染色质
死亡相关蛋白6
异染色质蛋白1
染色质
胚胎干细胞
细胞生物学
表观基因组
DNA甲基化
遗传学
DNA
基因
转录因子
核蛋白
基因表达
作者
Antoine Canat,Adeline Veillet,Renaud Batrin,Christèle Dubourg,Priscillia Lhoumaud,Pol Arnau-Romero,Maxim V. C. Greenberg,Frédéric Bonhomme,Paola B. Arimondo,Robert S. Illingworth,Emmanuelle Fabre,Pierre Therizols
摘要
Genomes comprise a large fraction of repetitive sequences folded into constitutive heterochromatin, which protect genome integrity and cell identity. De novo formation of heterochromatin during preimplantation development is an essential step for preserving the ground-state of pluripotency and the self-renewal capacity of embryonic stem cells (ESCs). However, the molecular mechanisms responsible for the remodeling of constitutive heterochromatin are largely unknown. Here, we identify that DAXX, an H3.3 chaperone essential for the maintenance of mouse ESCs in the ground state, accumulates in pericentromeric regions independently of DNA methylation. DAXX recruits PML and SETDB1 to promote the formation of heterochromatin, forming foci that are hallmarks of ground-state ESCs. In the absence of DAXX or PML, the three-dimensional (3D) architecture and physical properties of pericentric and peripheral heterochromatin are disrupted, resulting in de-repression of major satellite DNA, transposable elements and genes associated with the nuclear lamina. Using epigenome editing tools, we observe that H3.3, and specifically H3.3K9 modification, directly contribute to maintaining pericentromeric chromatin conformation. Altogether, our data reveal that DAXX is crucial for the maintenance and 3D organization of the heterochromatin compartment and protects ESC viability.
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