Pharmacoepigenetics of EZH2 Inhibitors

Abstract

Abstract First described in Drosophila melanogaster, polycomb group (PcG) and later trithorax group (trxG) genes were shown to serve in the preservation and maintenance of gene expression programs that modulate cellular differentiation, with roles as gene repressors and activators, respectively. PcG proteins are composed of two known chromatin-associating complexes: polycomb-repressive complex 1 (PRC1) and polycomb-repressive complex 2 (PRC2). EZH2 is the catalytic subunit within PRC2 responsible for the trimethylation of histone 3 lysine 27 and, with the aid of PRC1, EZH2 regulates transcriptional processes involved in cell proliferation, differentiation, and cell cycle progression. Disregulation of, and mutations within, EZH2 are known to lead to various disease states including a variety of cancers. Herein we describe the regulation of EZH2, PRC2-mediated EZH2 targets, EZH2 targets outside PRC2, common EZH2 mutations, viral interactions of EZH2, and EZH2 inhibitors.