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Cohen I; Zhao D; Bar C; Valdes V; Dauber-Decker K; Nguyen M; Nakayama M; Rendl M; Bickmore W; Koseki H; Zheng D; Ezhkova E (2018)

PRC1 FINE-TUNES GENE REPRESSION AND ACTIVATION TO SAFEGUARD SKIN DEVELOPMENT AND STEM CELL SPECIFICATION

CELL STEM CELL ():
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© 2018 Elsevier Inc. Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable. Further dissection demonstrated that both canonical and non-canonical PRC1 complexes bind to repressed genes, marked by H2AK119ub and PRC2-mediated H3K27me3. Interestingly, loss of canonical PRC1, PRC1 catalytic activity, or PRC2 leads to expansion of mechanosensitive Merkel cells in neonatal skin. Non-canonical PRC1 complexes, however, also bind to and promote expression of genes critical for skin development and SC formation. Together, our findings highlight PRC1's diverse roles in executing a precise developmental program. Cohen et al. show that Polycomb repressive complex 1 (PRC1), a critical chromatin regulator, is essential for skin epithelium morphogenesis and stem cell specification. By coupling in vivo chromatin and transcriptional profiling with loss-of-function studies, the authors show that PRC1 controls skin development through regulation of silent and active genes.