Abstract
Polycomb group (PcG) and Trithorax group (TrxG) proteins are epigenetic regulators that control gene expression through modulating chromatin structure and addition of posttranslational modifications (PTMs) on histones. They often act antagonistically and have opposite roles in regulating key genes involved in normal development and tumorigenesis. PcG complexes catalyze the deposition of repressive marks, H3K27 methylation and H2A119 ubiquitylation, to inhibit gene expression. In contrast, TrxG complexes methylate H3K4 to activate transcription, and some members also have ATP-dependent chromatin remodeling activities. In this review, we discuss our current understanding of the molecular mechanisms employed by TrxG and PcG proteins, as well as their biological functions in stem cells, differentiation and cancer. We will also highlight the importance and prevalence of crosstalk between TrxG/PcG proteins and other epigenetic machineries in gene regulation, including the impact of preexisting H3 PTMs on the activities of TrxG/PcG complexes. The emerging picture indicates that these epigenetic regulators are dynamically regulated by upstream signaling pathways, and they function in transmitting cellular signals to chromatin to mediate downstream nuclear processes.
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