RYBP and Cbx7 Define Specific Biological Functions of Polycomb Complexes in Mouse Embryonic Stem Cells

SummaryThe Polycomb repressive complex 1 (PRC1) is required for decisions of stem cell fate. In mouse embryonic stem cells (ESCs), two major variations of PRC1 complex, defined by the mutually exclusive presence of Cbx7 or RYBP, have been identified. Here, we show that although the genomic localization of the Cbx7- and RYBP-containing PRC1 complexes overlaps in certain genes, it can also be mutually exclusive. At the molecular level, Cbx7 is necessary for recruitment of Ring1B to chromatin, whereas RYBP enhances the PRC1 enzymatic activity. Genes occupied by RYBP show lower levels of Ring1B and H2AK119ub and are consequently more highly transcribed than those bound by Cbx7. At the functional level, we show that genes occupied by RYBP are primarily involved in the regulation of metabolism and cell-cycle progression, whereas those bound by Cbx7 predominantly control early-lineage commitment of ESCs. Altogether, our results indicate that different PRC1 subtypes establish a complex pattern of gene regulation that regulates common and nonoverlapping aspects of ESC pluripotency and differentiation.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► RYBP-PRC1 and Cbx7-PRC1 regulate a cohort of both common and specific sets of genes ► The presence of either RYBP or Cbx7 defines the biological function of PRC1 complexes ► PRC1-RYBP target genes are more highly expressed than PRC1-Cbx7 targets ► RYBP enhances PRC1 enzymatic activity, yet Cbx7 plays a pivotal role in PRC1 recruitment