Polycomb repressive complexes (PRCs) are essential chromatin regulators of cell identity. PRC1, which is a dominant executer of Polycomb-mediated control, possesses catalyticdependent H2AK119 mono-ubiquitination and catalytic-independent activities. Despite extensive knowledge of PRC1s role in embryonic stem cells (SCs), its function in somatic SCs and tissue development is largely unknown. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes in epidermal progenitors. Through loss-of-function studies, we show that global PRC1 function is essential for skin development and SC specification, whereas PRC1 catalytic activity is dispensable. By dissecting molecular mechanisms, we show that PRC1 catalytic-dependent and -independent activities repress non-skin lineage genes and attenuate expression of differentiation and proliferation genes. Interestingly, PRC1 also binds to and promotes the expression of critical skin developmental and SC genes independently of its catalytic activities. Our findings highlight PRC1s diverse roles in executing a precise developmental program.
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Polycomb repressive complexes (PRCs) are essential chromatin regulators of cell identity. PRC1, which is a dominant executer of Polycomb-mediated control, possesses catalyticdependent H2AK119 mono-ubiquitination and catalytic-independent activities. Despite extensive knowledge of PRC1s role in embryonic stem cells (SCs), its function in somatic SCs and tissue development is largely unknown. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes in epidermal progenitors. Through loss-of-function studies, we show that global PRC1 function is essential for skin development and SC specification, whereas PRC1 catalytic activity is dispensable. By dissecting molecular mechanisms, we show that PRC1 catalytic-dependent and-independent activities repress non-skin lineage genes and attenuate expression of differentiation and proliferation genes. Interestingly, PRC1 also binds to and promotes the expression of critical skin developmental and SC genes independently of its catalytic activities. Our findings highlight PRC1s diverse roles in executing a precise developmental program.
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