Polycomb complexes PRC1 and their function in hematopoiesis

•Polycomb PRC1 complexes are chromatin modifiers with histone H2A E3 ligase activity.•Canonical PRC1 compresses chromatin, noncanonical PRC1-containing DNA-binding subunits.•PRC1 targets in differentiated cells are transcriptionally repressed and active.•Both hematopoietic differentiation and homeostasis are regulated by PRC1.•PRC1 subunits promote/restrict hematopoietic transformation in a cell-context-specific manner.

Hematopoiesis, the process by which blood cells are continuously produced, is one of the best studied differentiation pathways. Hematological diseases are associated with reiterated mutations in genes encoding important gene expression regulators, including chromatin regulators. Among them, the Polycomb group (PcG) of proteins is an essential system of gene silencing involved in the maintenance of cell identities during differentiation. PcG proteins assemble into two major types of Polycomb repressive complexes (PRCs) endowed with distinct histone-tail-modifying activities. PRC1 complexes are histone H2A E3 ubiquitin ligases and PRC2 trimethylates histone H3. Established conceptions about their activities, mostly derived from work in embryonic stem cells, are being modified by new findings in differentiated cells. Here, we focus on PRC1 complexes, reviewing recent evidence on their intricate architecture, the diverse mechanisms of their recruitment to targets, and the different ways in which they engage in transcriptional control. We also discuss hematopoietic PRC1 gain- and loss-of-function mouse strains, including those that model leukemic and lymphoma diseases, in the belief that these genetic analyses provide the ultimate test for molecular mechanisms driving normal hematopoiesis and hematological malignancies.