Structural heterogeneity of the mammalian polycomb repressor complex in immune regulation

Abstract

Epigenetic regulation is mainly mediated by enzymes that can modify the structure of chromatin by altering the structure of DNA or histones. Proteins involved in epigenetic processes have been identified to study the detailed molecular mechanisms involved in the regulation of specific mRNA expression. Evolutionarily well-conserved polycomb group (PcG) proteins can function as transcriptional repressors by the trimethylation of histone H3 at the lysine 27 residue (H3K27me3) and the monoubiquitination of histone H2A at the lysine 119 residue (H2AK119ub). PcG proteins form two functionally distinct protein complexes: polycomb repressor complex 1 (PRC1) and PRC2. In mammals, the structural heterogeneity of each PRC complex is dramatically increased by several paralogs of its subunit proteins. Genetic studies with transgenic mice along with RNA-seq and chromatin immunoprecipitation (ChIP)-seq analyses might be helpful for defining the cell-specific functions of paralogs of PcG proteins. Here, we summarize current knowledge about the immune regulatory role of PcG proteins related to the compositional diversity of each PRC complex and introduce therapeutic drugs that target PcG proteins in hematopoietic malignancy. Immunology: Gene repressors regulating immunity offer cancer drug targets Protein complexes that suppress gene activity by remodeling chromatin, the substance that contains most of a cell's DNA, play a critical role in regulating the immune system and provide a therapeutic target for treating blood cancers. Seok-Jin Kang and Taehoon Chun from Korea University in Seoul, South Korea, review how polycomb group proteins, best known for their function in embryonic development, also contribute to the formation of immune cells from blood stem cell precursors. Studies with stem cells and cancer cells have begun to reveal many targets of these proteins, and drug companies are evaluating candidate agents directed against some polycomb group proteins in patients with lymphoma and other cancers. More comprehensive profiling of protein function across a broad range of immune cell types could reveal new targets for additional diseases associated with immune dysfunction.