MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells.

Polycomb repressive complex 1.6 (PRC1.6), one of the PRC1 subtypes, plays crucial roles in preventing the ectopic expression of meiosis-related genes in mouse embryonic stem cells (ESCs). In addition to the histone modifications H2AK119ub1 and H3K27me3 that are deposited by PRC1 and PRC2, respectively, many meiosis-related genes bear the trimethylated lysine 9 of histone H3 (H3K9me3) mark in ESCs. However, the precise molecular mechanisms that deposit this mark on these genes in ESCs remain unknown. Here, we demonstrated that MGA, a scaffolding component of PRC1.6, is directly involved in recruiting SETDB1, an enzyme that catalyzes this histone modification, via its interaction with ATF7IP. Thus, our findings indicate that MGA plays a dual role, first being central in establishing a PRC1/PRC2-dependent repressive state by contributing to the construction of PRC1.6 as a scaffolding component, and then inducing a more robustly repressed state by recruiting the STEDB1/ATF7IP complex for H3K9me3 modification.