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.

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。尽管 Polycomb 抑制复合物 (PRC) 1 和 PRC2 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 PRC1 或 PRC2 的小鼠胚胎。在这里，我们证明任一 PRC 的丢失对胚胎外组织中非活性 X 染色体 (Xi) 上基因沉默的维持具有重大影响，受影响的基因重叠但不同，表明这两个复合物可能具有独立的作用。重要的是，缺少 PRC1 不会影响 PRC2/H3K27me3 的积累，缺少 PRC2 也不会影响 PRC1/H2AK119ub1 在 Xi 上的积累。