H2AK119ub

Histone H2A lysine 119 ubiquitination, referred to as H2AK119ub1, is a post-translational modification in which a single ubiquitin molecule is attached to lysine 119 of histone H2A. In mammals, this mark is deposited primarily by the Polycomb Repressive Complex 1 (PRC1).

PRC1 is a family of complexes that include the E3 ubiquitin ligase subunits RING1A or RING1B and cofactors such as BMI1 or MEL-18, along with additional subunits that define canonical versus non-canonical PRC1 forms. Upon catalysis, H2AK119ub1 promotes a repressed chromatin state by limiting transcriptional initiation and contributing to chromatin compaction. It also assists in the recruitment or stabilization of other silencing components, including PRC2, which deposits H3K27me3, thereby supporting maintenance of Polycomb target gene silencing.

Genomically, H2AK119ub1 is enriched at promoters of developmentally regulated genes targeted by Polycomb and often co-localizes with H3K27me3. In embryonic stem cells, certain Polycomb target regions exhibit a bivalent chromatin configuration, with both repressive marks and activating marks in poised states.

Dynamic regulation occurs through deubiquitination by enzymes such as BAP1, part of the PR-DUB complex, which removes H2AK119ub1 to permit transcriptional activation when appropriate.

Functionally, H2AK119ub1 is important for proper development; disruption of PRC1 activity or misregulation of this mark is linked to developmental abnormalities and cancer. It also participates in X-chromosome inactivation as part of Polycomb-mediated silencing.