Polycomb repressive complexes 1 and 2 are each essential for maintenance of X inactivation in extra-embryonic lineages

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.

Authors: Masui O, Corbel, C, Nagao K,.Endo TA, Kezuka F, Diabangouaya P, Nakayama M, Kumon M, Koseki Y, Obuse C, Koseki H, Heard E

Journal: nature cell biology. 2023; 25:134–144.

DOI: https://doi.org/10.1038/s41556-022-01047-y