Abstract:
Activation-induced cytidine deaminase (AID) is responsible for the initiation of somatic hypermutation (SHM) and class-switch recombination (CSR), which result in antibody affinity maturation and isotype switching, thus producing pathogen-specific antibodies. Chromatin dynamics and accessibility play a significant role in determining AID expression and its targeting. Chromatin remodelers contribute to the accessibility of the chromatin structure, thereby influencing the targeting of AID to Ig genes. Epigenetic modifications, including DNA methylation, histone modifications, and miRNA expression, profoundly impact the regulation of AID and chromatin remodelers targeting Ig genes. Additionally, epigenetic modifications lead to chromatin rearrangement and thereby can change AID expression levels and its preferential targeting to Ig genes. This interplay is symbolized as the ACE phenomenon encapsulates three interconnected aspects: AID, Chromatin remodelers, and Epigenetic modifications. This review emphasizes the importance of understanding the intricate relationship between these aspects to unlock the therapeutic potential of these molecular processes and molecules.
摘要:
激活诱导的胞苷脱氨酶(AID)负责启动体细胞超突变(SHM)和类别转换重组(CSR),导致抗体亲和力成熟和同种型转换,从而产生病原体特异性抗体。染色质动力学和可及性在确定AID表达及其靶向中起重要作用。染色质重塑剂有助于染色质结构的可及性,从而影响AID对Ig基因的靶向。表观遗传修饰,包括DNA甲基化,组蛋白修饰,和miRNA表达,深刻影响AID和针对Ig基因的染色质重塑的调控。此外,表观遗传修饰导致染色质重排,从而可以改变AID表达水平及其对Ig基因的优先靶向。这种相互作用被象征为ACE现象封装了三个相互关联的方面:AID,染色质重塑剂,和表观遗传修饰。这篇综述强调了理解这些方面之间复杂关系以解锁这些分子过程和分子的治疗潜力的重要性。