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Polycomb-repressive complex 1 (PRC1) and PRC2 are critical chromatin regulators of gene expression and tissue development. Here, we show that despite extensive genomic cobinding, PRC1 is essential for epidermal integrity, whereas PRC2 is dispensable. Loss of PRC1 resulted in blistering skin, reminiscent of human skin fragility syndromes. Conversely, PRC1 does not restrict epidermal stratification during skin morphogenesis, whereas PRC2 does. Molecular dissection demonstrated that PRC1 functions with PRC2 to silence/dampen expression of adhesion genes. In contrast, PRC1 promotes expression of critical epidermal adhesion genes independently of PRC2-mediated H3K27me3. Together, we demonstrate a functional link between epigenetic regulation and skin diseases.

PRC1 preserves epidermal tissue integrity independently of PRC2