Zhang Yunfei, Fan Yufeng, Hu Ying, Wang Xiaocui, Wen Bin, Duan Xuemei, Li Haonan, Dong Shumin, Yan Ze, Zhang Weiwei, Jing Yukai
Department of Clinical Laboratory, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
Department of Anesthesiology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
Cell Death Discov. 2025 Jun 19;11(1):280. doi: 10.1038/s41420-025-02563-0.
DNA methylation is a key epigenetic modification that regulates gene expression, cell differentiation, and genome stability. Aberrant DNA methylation patterns, including the hypermethylation or global hypomethylation of tumor suppressor genes, are strongly associated with various human diseases, such as cancer, autoimmune disorders, and metabolic syndrome. DNA methylation predominantly occurs at CpG dinucleotides, influencing transcription by altering chromatin structure and accessibility. MBD2 (Methyl-CpG-binding proteins 2) play a crucial role in interpreting these epigenetic marks and regulating downstream gene expression. In disease contexts, aberrant DNA methylation disrupts cellular homeostasis by silencing key regulatory genes or activating pathological pathways. Current research primarily focuses on MBD2 in cancer, with less emphasis on its role in autoimmune diseases. This review discusses the role of MBD2 in regulating immune cell development and differentiation through epigenetic mechanisms, particularly DNA methylation and its regulatory components. Furthermore, it highlights the mechanistic contributions of MBD2 to autoimmune diseases such as systemic lupus erythematosus and evaluates its potential as a novel therapeutic target for these conditions.
DNA甲基化是一种关键的表观遗传修饰，可调节基因表达、细胞分化和基因组稳定性。异常的DNA甲基化模式，包括肿瘤抑制基因的高甲基化或整体低甲基化，与各种人类疾病密切相关，如癌症、自身免疫性疾病和代谢综合征。DNA甲基化主要发生在CpG二核苷酸处，通过改变染色质结构和可及性来影响转录。MBD2（甲基-CpG结合蛋白2）在解读这些表观遗传标记和调节下游基因表达中起着关键作用。在疾病背景下，异常的DNA甲基化通过使关键调节基因沉默或激活病理途径来破坏细胞稳态。目前的研究主要集中在MBD2在癌症中的作用，而较少强调其在自身免疫性疾病中的作用。这篇综述讨论了MBD2通过表观遗传机制，特别是DNA甲基化及其调节成分，在调节免疫细胞发育和分化中的作用。此外，它强调了MBD2对系统性红斑狼疮等自身免疫性疾病的机制贡献，并评估了其作为这些疾病新型治疗靶点的潜力。
