Female mammals inherit two X chromosomes from their parents whereas males inherit a single X chromosome and a Y chromosome. To equalise gene dosage, XX females silence one of the two X chromosomes. This process called X inactivation is regulated by a long non-coding RNA Xist, which coats the inactive chromosome in cis and recruits chromatin modifiers and RNA-binding proteins to promote chromosome silencing. The Polycomb complexes PRC1 and PRC2 are chromatin modifiers that are recruited rapidly in response to Xist expression. Almeida et al. identified PCGF3/5-PRC1 complexes as indispensable initiators for Polycomb recruitment to the inactive X chromosome, and further clarify molecular mechanisms that lead to the subsequent enrichment of other Polycomb complexes. Additionally, the authors demonstrate that Polycomb recruitment is critical for Xist-mediated chromosome silencing and mouse female embryogenesis.

Photo: Lack of enrichment of Polycomb deposited marks (H2AK119u1 by PRC1 in green, H3K27me3 by PRC2 in red) over the inactive X chromosome in Pcgf3 Pcgf5 double knockout (on the right) compared to a wild-type female embryo (on the left). Image: Tatyana B. Nesterova/ Mafalda Almeida