Activity of PRC1 and Histone H2AK119 Monoubiquitination: Revising Popular Misconceptions

Polycomb group proteins are evolutionary conserved chromatin-modifying complexes, essential for the regulation of developmental and cell-identity genes. Polycomb-mediated transcriptional regulation is provided by two multi-protein complexes known as Polycomb repressive complex 1 (PRC1) and 2 (PRC2). Recent studies positioned PRC1 as a foremost executer of Polycomb-mediated transcriptional control. Mammalian PRC1 complexes can form multiple sub-complexes that vary in their core and accessory subunit composition, leading to fascinating and diverse transcriptional regulatory mechanisms employed by PRC1 complexes. These mechanisms include PRC1-catalytic activity toward monoubiquitination of histone H2AK119, a well-established hallmark of PRC1 complexes, whose importance has been long debated. In this review, the central roles that PRC1-catalytic activity plays in transcriptional repression are emphasized and the recent evidence supporting a role for PRC1 complexes in gene activation is discussed.