Abstract
Polycomb group (PcG) proteins function as chromatin-based transcriptional repressors
that are essential for normal gene regulation during development. However, how these systems
function to achieve transcriptional regulation remains very poorly understood. Here, we discover
that the histone H2AK119 E3 ubiquitin ligase activity of Polycomb repressive complex 1 (PRC1) is
defined by the composition of its catalytic subunits and is highly regulated by RYBP/YAF2-
dependent stimulation. In mouse embryonic stem cells, RYBP plays a central role in shaping
H2AK119 mono-ubiquitylation at PcG targets and underpins an activity-based communication
between PRC1 and Polycomb repressive complex 2 (PRC2) which is required for normal histone H3
lysine 27 trimethylation (H3K27me3). Without normal histone modification-dependent
communication between PRC1 and PRC2, repressive Polycomb chromatin domains can erode,
rendering target genes susceptible to inappropriate gene expression signals. This suggests that
activity-based communication and histone modification-dependent thresholds create a localized
form of epigenetic memory required for normal PcG chromatin domain function in gene regulation.
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