PRC1PRDUB

PRC1PRDUB is a chromatin‑associated protein complex that integrates features of the Polycomb Repressive Complex 1 (PRC1) with the deubiquitinase activity of the PR‑DUB (Polycomb Repressive Deubiquitinase) module. It is essential for maintaining transcriptional repression of developmental genes and for cell‑state transitions through the precise regulation of histone modifications. The complex is composed of the canonical PRC1 core proteins RING1A/B, PCGF1/3/5/6, a CBX family chromobox protein, and the PR‑DUB subunits ASXL1 or ASXL2 together with the deubiquitinase BAP1. PRC1PRDUB functions to remove monoubiquitin from histone H2A at lysine 119 (H2AK119ub1), a mark placed by PRC1, thereby creating a feedback loop that modulates chromatin compaction and gene silencing.

During spermatogenesis and early embryonic development, PRC1PRDUB activity is dynamically regulated, forming specific subcomplexes that act in a cell‑type–specific manner. The complex directly binds to target gene promoters and enhancer elements, coordinating with SWI/SNF complexes to modulate chromatin accessibility. Perturbation of PRC1PRDUB components has been linked to a range of developmental disorders and cancers, including acute myeloid leukemia and posterior cortical atrophy, likely due to derepression of oncogenic pathways. Recent structural studies have mapped the interface between ASXL1 and BAP1, revealing potential sites for therapeutic intervention that could selectively disrupt aberrant PRC1PRDUB activity without affecting normal chromatin regulation.