Epigenetic regulation of T cells by Polycomb group proteins

Abstract

T cells are critical for pathogen elimination, tumor surveillance, and immunoregulation. The development, activation, and differentiation of CD8 and CD4 T lymphocytes are a set of complex and dynamically regulated events that require epigenetic control. The Polycomb group (PcG) proteins are a family of diverse and evolutionarily conserved epigenetic modulators fundamentally involved in several mechanisms of gene regulation. PcG proteins can assemble into distinct repressor complexes, the two most understood being the Polycomb Repressor Complex (PRC)1 and PRC2, which control chromatin structure mainly through posttranslational modifications of histones. In this review, we will summarize the most recent findings regarding the diverse roles performed by PcG proteins in T cell biology. We will focus on PRC1 and PRC2 contribution to the regulation of T cell development in the thymus, CD4 T cell differentiation in helper or regulatory phenotypes and CD8 T cell fate commitment in the context of infections and cancer, highlighting the known mechanisms and knowledge gaps that still need to be addressed.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development

“…PRC1 is associated with tumor proliferation, metastasis, and tumorigenesis. It is highly expressed in multiple tumors and is regulated by nuclear β-catenin and WNT expression[ 62 ]. Additionally, some studies have reported that PRC1 controls chromatin structure mainly through posttranslational histone modifications.…”

Polycomb Repressive Complex 1 subunit Cbx4 positively regulates effector responses in CD8 T cells

“…H3K27me3 can recruit another epigenetic complex from the Polycomb group (PcG), the PRC1, that also works as a repressor through the ubiquitylation of lysine 119 of histone H2A (H2AK119ub) by its catalytic subunit Ring1, as well as through chromatin remodeling mechanisms mediated by other subunits that can integrate the complex (32). PRC1 composition is highly heterogeneous, and its distinct configurations are divided in canonical (cPRC1) or noncanonical PRC1 (ncPRC1) (33, 34). While ncPRC1 complexes can be recruited to genome sites independently of PRC2 function (35, 36), cPRC1 are known to be recruited to H3K27me3-tagged loci .…”