Saurav Sharma, Mallar Dasgupta, Bindu Sai Vadaga, Prashant Kodgire
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引用次数: 0
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.
激活诱导胞苷脱氨酶（AID）负责启动体细胞超突变（SHM）和类开关重组（CSR），从而导致抗体亲和力成熟和同种型切换，进而产生病原体特异性抗体。染色质动力学和可及性在决定 AID 表达及其靶向性方面起着重要作用。染色质重塑因子有助于提高染色质结构的可及性，从而影响 AID 对 Ig 基因的靶向性。表观遗传修饰（包括 DNA 甲基化、组蛋白修饰和 miRNA 表达）对 AID 和染色质重塑因子靶向 Ig 基因的调控有深远影响。此外，表观遗传修饰会导致染色质重排，从而改变 AID 的表达水平及其对 Ig 基因的优先靶向性。这种相互作用被称为 ACE 现象，它包含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错综复杂的关系对于发掘这些分子过程和分子的治疗潜力的重要性。
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