Abstract
T cell lineage decisions are critical for the development of proper immune responses to pathogens as well as important for the resolution of inflammatory responses. This differentiation process relies on a combination of intrinsic and extrinsic factors converging upon epigenetic regulation of transcriptional networks relevant to specific T cell lineages. As these biochemical modifications represent therapeutic opportunities in cancer biology and autoimmunity, implications of writers and readers of epigenetic marks to immune cell differentiation and function are highly relevant. Given the ready adoption of histone methyltransferase inhibitors in the clinic, we focus this review on the role of three histone modifying complexes: PRC-1, PRC-2, and G9A in modulating T cell fate decisions. Furthermore, we explore the role of long non-coding RNAs in regulating these processes, and discuss recent advances and challenges of implementing epigenetic therapies into clinical practice.
Highlights
The immune system comprises a large number of cell types that have the ability to respond to external environmental cues and adopt a wide variety of cell fates
We explore the role of long non-coding RNAs in regulating these processes, and discuss recent advances and challenges associated with implementing epigenetic therapies in clinical practice
The Polycomb-Group proteins, Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2), mediate post-translational modifications (PTMs) of histones required for cell differentiation and development through the regulation of chromatin structure and gene expression
Summary
The immune system comprises a large number of cell types that have the ability to respond to external environmental cues and adopt a wide variety of cell fates. While recent clinical trials have demonstrated a favorable safety profile of selective inhibition of EZH2 [6], a comprehensive understanding of the role that epigenetic modifying complexes play in the development and function of different immune cell types is relevant to the development and safety of epigenetic therapeutics. The Polycomb-Group proteins, Polycomb Repressive Complex 1 (PRC1) and 2 (PRC2), mediate post-translational modifications (PTMs) of histones required for cell differentiation and development through the regulation of chromatin structure and gene expression.
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