Histone Acetylation and the Regulation of Major Histocompatibility Class II Gene Expression.

Abstract

Major histocompatibility complex (MHC) class II molecules are essential for processing and presenting exogenous pathogen antigens to activate CD4+ T cells. Given their central role in adaptive immune responses, MHC class II genes are tightly regulated in a tissue- and activation-specific manner. The regulation of MHC class II gene expression involves various transcription factors that interact with conserved proximal cis-acting regulatory promoter elements, as well as MHC class II transactivator that interacts with a variety of chromatin remodeling machineries. Recent studies also identified distal regulatory elements within MHC class II gene locus that provide enormous insight into the long-range coordination of MHC class II gene expression. Novel therapeutic modalities that can modify MHC class II genes at the epigenetic level are emerging and are currently in preclinical and clinical trials. This review will focus on the role of chromatin remodeling, particularly remodeling that involves histone acetylation, in the constitutive and inducible regulation of MHC class II gene expression.