Polycomb repressive complexes 1 and 2 are each essential for maintenance of X inactivation in extra-embryonic lineages
Polycomb repressive complexes 1 and 2 are each essential for maintenance of X inactivation in extra-embryonic lineages
复制标题
Polycomb 抑制复合物 1 和 2 对于维持胚胎外谱系中的 X 失活至关重要
DOI：
10.1038/s41556-022-01047-y
复制
发表时间：
2023
影响因子：
21.3
通讯作者：
Heard Edith
中科院分区：
文献类型：
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作者：
Masui Osamu;Corbel Catherine;Nagao Koji;Endo Takaho A.;Kezuka Fuyuko;Diabangouaya Patricia;Nakayama Manabu;Kumon Mami;Koseki Yoko;Obuse Chikashi;Koseki Haruhiko;Heard Edith
在雌性哺乳动物中，两条X染色体中的一条在发育过程中因X染色体失活（XCI）而失活。虽然Polycomb抑制复合物（PRC）1和PRC 2都与基因沉默有关，但它们在体内发育过程中在XCI中的确切作用仍然难以捉摸。为此，我们研究了缺乏PRC 1或PRC 2的小鼠胚胎。在这里，我们证明，无论是PRC的损失有实质性的影响，维持基因沉默的非活性X染色体（Xi）在胚胎外组织，与重叠，但不同的基因受影响，表明潜在的独立作用的两个复合物。重要的是，PRC 1的缺乏不影响PRC 2/H3 K27 me 3的积累，PRC 2的缺乏不影响PRC 1/H2 AK 119 ub 1在Xi上的积累。因此，PRC 1和PRC 2独立地有助于在早期植入后胚外谱系中维持XCI，揭示了两种Polycomb复合物都可以直接参与XCI并且在XCI中不同地部署。
In female mammals, one of the two X chromosomes becomes inactivated during development by X-chromosome inactivation (XCI). Although Polycomb repressive complex (PRC) 1 and PRC2 have both been implicated in gene silencing, their exact roles in XCI during in vivo development have remained elusive. To this end, we have studied mouse embryos lacking either PRC1 or PRC2. Here we demonstrate that the loss of either PRC has a substantial impact on maintenance of gene silencing on the inactive X chromosome (Xi) in extra-embryonic tissues, with overlapping yet different genes affected, indicating potentially independent roles of the two complexes. Importantly, a lack of PRC1 does not affect PRC2/H3K27me3 accumulation and a lack of PRC2 does not impact PRC1/H2AK119ub1 accumulation on the Xi. Thus PRC1 and PRC2 contribute independently to the maintenance of XCI in early post-implantation extra-embryonic lineages, revealing that both Polycomb complexes can be directly involved and differently deployed in XCI.