biostudies-literatureMoussa HFNCI NIH HHSNIGMS NIH HHS1931https://www.ebi.ac.uk/biostudies/studies/S-EPMC6488670biostudies-literatureUnknown10(1)Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, promNature communicationsCanonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing.PMC6488670R01 GM100919R01 CA218392Bsteh DMichetti LStecher KYelagandula RElling UZepeda-Martinez JAWang JStuckey JIJames LIBartalska KBell OPribitzer CMoussa HFFrye SVfalseCanonical PRC1 controls sequence-independent propagation of Polycomb-mediated gene silencing.Polycomb group (PcG) proteins play critical roles in the epigenetic inheritance of cell fate. The Polycomb Repressive Complexes PRC1 and PRC2 catalyse distinct chromatin modifications to enforce gene silencing, but how transcriptional repression is propagated through mitotic cell divisions remains a key unresolved question. Using reversible tethering of PcG proteins to ectopic sites in mouse embryonic stem cells, here we show that PRC1 can trigger transcriptional repression and Polycomb-dependent chromatin modifications. We find that canonical PRC1 (cPRC1), but not variant PRC1, maintains gene silencing through cell division upon reversal of tethering. Propagation of gene repression is sustained by cis-acting histone modifications, PRC2-mediated H3K27me3 and cPRC1-mediated H2AK119ub1, prom2019-01-01T00:00:00Z2019 Apr2026-05-07T10:29:08.932Z2019-06-06T22:50:31ZS-EPMC64886703103680410.1038/s41467-019-09628-6