EZH1 and EZH2 Co-Govern Histone H3K27 Trimethylation and Are Essential for Hair Follicle Homeostasis and Wound Repair

The study investigated the roles of H3K27 methyltransferases Ezh2 and Ezh1 in mouse skin homeostasis by conditionally targeting these enzymes. It was found that the absence of both Ezh1 and Ezh2 led to the loss of H3K27me3, causing hair follicles to arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, while the epidermis showed hyperproliferation and survived. Despite these differences, similar genes were up-regulated in both hair follicle and epidermal Ezh1/2-null progenitors, particularly nonskin lineage genes and the Ink4a/Inkb/Arf locus. The study highlighted that the full activation of Ink4a/Arf/Ink4b genes in hair follicle cells, but only partial activation in epidermal progenitors, was significant. Importantly, restoring proliferation and survival of Ezh1/2-null hair follicle progenitors in vitro was possible by targeting the Ink4b/Ink4a/Arf locus, underscoring its relevance to the observed phenotypes. This research provided new insights into Polycomb-dependent tissue control and the differential response of progenitors to the loss of H3K27me3.