Activity of PRC1 and Histone H2AK119 Monoubiquitination: Revising Popular Misconceptions

Abstract 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.