RYBP/YAF2-PRC1 Complex and H1-dependent Chromatin Compaction Mediate Propagation of H2AK119ub1 during Cell Division

Stable propagation of epigenetic information is important for maintaining the cell identity in multicellular organisms. However, it remains largely unknown how H2AK119ub1 is established and stably propagated during cell division. In this study, we found that RYBP/YAF2 specifically binds H2AK119ub1, then recruits RYBP/YAF2-PRC1 complex to catalyze the ubiquitylation of H2A on neighboring nucleosomes through a positive-feedback model. Additionally, we demonstrated that H1-compacted chromatin enhances the distal propagation of H2AK119ub1 and thereby reinforcing the inheritance of H2AK119ub1 during cell division. Moreover, we showed that either disruption of RYBP/YAF2-PRC1 activity or impairment of H1-dependent chromatin compaction resulted in a significant defect of the maintenance of H2AK119ub1. Therefore, our results suggest that H1-dependent chromatin compaction plays a critical role in the stable propagation of H2AK119ub1 by RYBP/YAF2-PRC1 during cell division.