Early discoveries in chromatin biology and epigenetics heralded new insights into organismal development. From these studies, two mediators of cellular differentiation were discovered: the Polycomb group (PcG) of transcriptional repressors, and the trithorax group (trxG) of transcriptional activators. These protein families, while opposed in function, work together to coordinate the appropriate cellular developmental programs that allow for both embryonic stem cell self-renewal and differentiation. Recently, both the PcG and trxG chromatin modulators have been observed to be deregulated in a wide spectrum diseases including developmental disorders and cancer. To understand the impact of these findings we outline the past, present, and future. WIREs Dev Biol 2016, 5:659-688. doi: 10.1002/wdev.244 For further resources related to this article, please visit the WIREs website.
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