Conway et al. show that BAP1 acts as an epigenomic ‘bookend’ to constrain Polycomb complexes and their repressive catalytic activities, imagined here as books, to promoter regions of the genome. When BAP1 is absent the Polycomb complexes and their associated histone modifications diffuse throughout the genome, illustrated on the cover as a fallen book from which chromatin is spilling, causing Polycomb target activation and chromatin compaction.

Artwork by Monica Conway. Digital editing by Ben Conway.

Tamburri et al. review the mechanisms and pathological implications related to the constant “fight” between PRC1 E3-ligase activity (envisioned as the greediness of Prince John in “accumulating” gold) and its removal by PR-DUB (represented by the ability of Robin Hood in “stealing” the gold and giving it to the poor) to maintain correct levels of histone H2AK119 ubiquitination. This review analyzes the molecular details of mutations affecting the “contenders” of this fight, found in cancer and neurodevelopmental disorders, an unbalancing of histone H2AK119 ubiquitination levels with specific pathological states.

Artwork by Miriam Corso and Simone Tamburri.

Conway et al. show antagonism, depicted as a boxing match, between sub-complexes of PRC2 defined by either the presence of PCL1-3 and PALI1 (PRC2.1) or JARID2 and AEBP2 (PRC2.2). This antagonism is caused by biochemical competition between sub-complex subunits for docking sites on core PRC2.

Artwork by Marlena Mucha.