Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russia.
Biomolecules. 2024 Sep 4;14(9):1117. doi: 10.3390/biom14091117.
This review deals with the functional characteristics and biological roles of enzymes participating in DNA methylation and demethylation as key factors in epigenetic regulation of gene expression. The set of enzymes that carry out such processes in human cells is limited to representatives of two families, namely DNMT (DNA methyltransferases) and TET (DNA dioxygenases). The review presents detailed information known today about each functionally important member of these families and describes the catalytic activity and roles in the mammalian body while also providing examples of dysregulation of the expression and/or activity of these enzymes in conjunction with the development of some human disorders, including cancers, neurodegenerative diseases, and developmental pathologies. By combining the up-to-date information on the dysfunction of various enzymes that control the DNA "methylome" in the human body, we hope not only to draw attention to the importance of the maintenance of a required DNA methylation level (ensuring epigenetic regulation of gene expression and normal functioning of the entire body) but also to help identify new targets for directed control over the activity of the enzymes that implement the balance between processes of DNA methylation and demethylation.
这篇综述探讨了参与 DNA 甲基化和去甲基化的酶的功能特性和生物学作用,这些酶是基因表达表观遗传调控的关键因素。在人类细胞中执行这些过程的酶集合仅限于两类家族的代表,即 DNMT(DNA 甲基转移酶)和 TET(DNA 双加氧酶)。该综述详细介绍了这些家族中每个功能重要成员的现有信息,并描述了它们在哺乳动物体内的催化活性和作用,同时还提供了这些酶的表达和/或活性失调与某些人类疾病(包括癌症、神经退行性疾病和发育病理学)发展相关的例子。通过结合有关控制人体“甲基组”的各种酶功能障碍的最新信息,我们不仅希望引起人们对维持所需 DNA 甲基化水平(确保基因表达的表观遗传调控和整个身体的正常功能)的重要性的关注,而且还希望有助于确定新的靶点,以便对实施 DNA 甲基化和去甲基化过程之间平衡的酶的活性进行定向控制。