SAM Domain Polymerization Links Subnuclear Clustering of PRC1 to Gene Silencing

The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically visible clusters in nuclei; however, the impact of this cluster formation on transcriptional regulation and the underlying mechanisms that regulate this process remain obscure. Here, we report that the sterile alpha motif (SAM) domain of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through head-to-tail macromolecular polymerization, which is associated with stable target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role for SAM domain polymerization in this repression by two distinct mechanisms: first, through capturing and/or retaining PRC1 at the PcG targets, and second, by strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional repression. Our findings reveal a regulatory mechanism mediated by SAM domain polymerization for PcG-mediated repression of developmental loci that enables a robust yet reversible gene repression program during development. [Display omitted] •PRC1 forms visible subnuclear clusters at its target loci in mouse primary cells•The polymerization of the Phc2 SAM domain is required for PRC1 clustering•Clustering of PRC1 links to chromatin condensation and gene silencing•PRC1 clustering associates with stable binding of PRC1/PRC2 at its target loci Gene silencing by the Polycomb-repressive complex-1 (PRC1) is crucial for embryogenesis. Isono et al. show that subnuclear PRC1 clustering at its target genes is mediated by the polymerization capacity of the Phc2 SAM domain and associates with stable PRC1/PRC2 binding, trimethylation of histone H3 Lys27, and robust gene silencing.