PPARγ and C/EBPα enable adipocyte differentiation upon inhibition of histone methyltransferase PRC2 in malignant tumors.

ABSTRACT: Loss of terminal differentiation is a hallmark of cancer and offers a potential mechanism for differentiation therapy. Polycomb repressive complex 2 (PRC2) serves as the methyltransferase for K27 of histone H3 that is crucial in development. While PRC2 inhibitors show promise in treating various cancers, the underlying mechanisms remain incompletely understood. Here, we demonstrated that the inhibition or depletion of PRC2 enhanced adipocyte differentiation in malignant rhabdoid tumors and mesenchymal stem cells, through upregulation of peroxisome proliferator-activated receptor gamma (PPARG) and CEBPA. Mechanistically, PRC2 directly represses their transcription through H3K27 methylation, as both genes exhibit a bivalent state in mesenchymal stem cells. KO of PPARG compromised C/EBPα expr

SUBMITTER: Zhao J 

PROVIDER: S-EPMC11533084 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature