Analysis of Polycomb Repressive Complexes binding dynamics during limb development reveals the prevalence of PRC2-independent PRC1 occupancy

Abstract

The Polycomb group (PcG) proteins are key players in the regulation of tissue-specific gene expression through their known ability to epigenetically silence developmental genes. The PcG proteins form two multicomponent complexes, Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2), whereby the hierarchical model of recruitment postulates that PRC2 triggers the trimethylation of Histone H3 lysine 27 (H3K27me3) leading to the recruitment of PRC1. Here we report on the genome-wide binding dynamics of components from both PRC1 and PRC2 in the developing limb. We show that a large proportion of PRC-bound promoters are occupied exclusively by PRC1, suggesting a more extensive PRC1-specific activity than anticipated. We found that PRC1 (RING1B) and PRC2 (SUZ12) co-occupy the promoters of developmental genes, for which a subset become up-regulated upon the inactivation of PRC2. Strikingly, we found that RING1B occupancy is largely unaffected by the loss of PRC2, revealing a complex functional relationship between these two complexes in regulating gene expression and possibly an expansive functional interplay between canonical and non-canonical PRC1.