Three Mechanisms by Which Epigenetic Regulators Can Control Inflammation
(A) Binding of BRD4 to acetylated p65 subunit of NF-κB leads to enhanced cyclin-dependent kinase 9 (CDK9)-mediated phosphorylation of RNA polymerase II (Pol II) and increased transcription of downstream proinflammatory genes. This provides a general mechanism by which BRD4 promotes inflammatory signaling in diverse cell types. (B) The lysine demethylases JMJD3 and UTX remove repressive H3K27 trimethylation marks at regulatory sites for proinflammatory genes in macrophages, thereby stimulating downstream target gene expression. (C) Acetylation of lysine residues in FoxP3 promotes its DNA binding and transcriptional activity, thereby leading to enhanced regulatory T cell (Treg) differentiation and anti-inflammatory function.