Suzuki K, Luo Y
Faculty of Medical Technology, Teikyo University, Itabashi, Japan.
Faculty of Medical Technology, Teikyo University, Itabashi, Japan.
Adv Protein Chem Struct Biol. 2017;106:71-111. doi: 10.1016/bs.apcsb.2016.08.002. Epub 2016 Sep 23.
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.
主要组织相容性复合体(MHC)II类分子对于处理和呈递外源性病原体抗原以激活CD4 T细胞至关重要。鉴于其在适应性免疫反应中的核心作用,MHC II类基因以组织和激活特异性的方式受到严格调控。MHC II类基因表达的调控涉及多种转录因子,这些转录因子与保守的近端顺式作用调控启动子元件相互作用,以及与多种染色质重塑机制相互作用的MHC II类反式激活因子。最近的研究还在MHC II类基因座内鉴定出远端调控元件,这为深入了解MHC II类基因表达的远程协调提供了巨大帮助。能够在表观遗传水平修饰MHC II类基因的新型治疗方法正在兴起,目前正处于临床前和临床试验阶段。本综述将重点关注染色质重塑的作用,特别是涉及组蛋白乙酰化的重塑在MHC II类基因表达的组成性和诱导性调控中的作用。