{"title":"DNA甲基化异常与代谢功能障碍相关性脂肪肝的发生有关","authors":"O. Abaturov, A. Nikulina, O. Rusakova","doi":"10.22141/2224-0551.19.4.2024.1710","DOIUrl":null,"url":null,"abstract":"The literature review deals with DNA methylation, a key epigenetic mechanism that controls the activity of gene transcription, plays a decisive role in the formation of genomic imprinting, gene silencing, X-chromosome inactivation, RNA splicing, DNA repair, cell differentiation and cell reprogramming, and also determines the occurrence and development of liver steatotic lesions and metabolic disorders. Methylation of DNA cytosine dinucleotide (CpG) can be represented in two types: de novo CpG methylation, which is carried out by 5mC DNA writers — DNA-(cytosine-5)-methyltransferase (DNMT) 3a and 3b, and supporting DNA methylation, which is performed by DNMT1 during DNA replication. It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to personalize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.","PeriodicalId":338009,"journal":{"name":"CHILD`S HEALTH","volume":"21 2","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Aberrant DNA methylation associated with the development of metabolic dysfunction-associated fatty liver disease\",\"authors\":\"O. Abaturov, A. Nikulina, O. 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It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to personalize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.\",\"PeriodicalId\":338009,\"journal\":{\"name\":\"CHILD`S HEALTH\",\"volume\":\"21 2\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CHILD`S HEALTH\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.22141/2224-0551.19.4.2024.1710\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CHILD`S HEALTH","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22141/2224-0551.19.4.2024.1710","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
DNA 甲基化是一种关键的表观遗传机制,它控制着基因转录的活性,在基因组印记的形成、基因沉默、X 染色体失活、RNA 剪接、DNA 修复、细胞分化和细胞重编程等方面起着决定性作用,还决定着肝脏脂肪变性病变和代谢紊乱的发生和发展。DNA 胞嘧啶二核苷酸(CpG)的甲基化可分为两种类型:一种是由 5mC DNA 写手--DNA-(胞嘧啶-5)甲基转移酶(DNMT)3a 和 3b 进行的新生 CpG 甲基化;另一种是由 DNMT1 在 DNA 复制过程中进行的支持性 DNA 甲基化。研究发现,维持 DNA 甲基化可在新一代细胞中保留祖细胞特有的甲基化模式,而基因体的 DNA 甲基化与其表达的增加有关。5mC 的主动去甲基化是由 TET 二氧化酶进行的,其中包括三种酶代表:TET1、TET2 和 TET3。研究表明,DNA 核苷酸的异常甲基化与脂质合成的活性、氧化应激的程度、肝脏脂肪变性的发展、低度炎症、胰岛素抵抗和肝纤维化的进展直接相关。作者详细介绍了 5mC 位点的 DNA 甲基转移酶、擦除器和阅读器的功能和特点;可能违反 5mC DNA 写入器和擦除器活性平衡的情况;DNA 甲基化景观和模式;DNA 甲基化特征在代谢功能障碍相关性脂肪肝中的临床意义。代谢功能障碍相关性脂肪肝患者的基因组(至少 55 个基因)出现全球性低甲基化。作者强调,DNA 甲基化特征的使用是代谢功能障碍相关性脂肪肝病程早期诊断和预后的一个很有前景的方向,而对参与基因表达调控的 DNA 甲基化机制的分子成分及其活性对暴露于暴露组的依赖性的研究,将有助于对代谢功能障碍相关性脂肪肝患者的生活方式和饮食调整提出个性化建议并加以改进。
Aberrant DNA methylation associated with the development of metabolic dysfunction-associated fatty liver disease
The literature review deals with DNA methylation, a key epigenetic mechanism that controls the activity of gene transcription, plays a decisive role in the formation of genomic imprinting, gene silencing, X-chromosome inactivation, RNA splicing, DNA repair, cell differentiation and cell reprogramming, and also determines the occurrence and development of liver steatotic lesions and metabolic disorders. Methylation of DNA cytosine dinucleotide (CpG) can be represented in two types: de novo CpG methylation, which is carried out by 5mC DNA writers — DNA-(cytosine-5)-methyltransferase (DNMT) 3a and 3b, and supporting DNA methylation, which is performed by DNMT1 during DNA replication. It has been found that the maintenance DNA methylation allows the preservation of the methylation pattern characteristic of progenitor cells in the cells of the new generation, and the DNA methylation of the gene body is associated with its increased expression. Active demethylation of 5mC is carried out by TET dioxygenases, including three enzymatic representatives: TET1, TET2 and TET3. It has been demonstrated that aberrant methylation of DNA nucleotides is directly related to the activity of lipid synthesis, the degree of oxidative stress, the development of liver steatosis, low-grade inflammation, insulin resistance, and the progression of liver fibrosis. The authors presented in detail the functions and features of DNA methyltransferases, erasers, and readers of 5mC sites; possible violations of the balance of activity of writers and erasers of 5mC DNA; DNA methylation landscape and patterns; clinical significance of DNA methylation signatures in metabolic dysfunction-associated fatty liver disease. Global hypomethylation of genome, at least 55 genes, is observed in patients with metabolic dysfunction-associated fatty liver disease. The authors emphasize that the use of DNA methylation signatures is a promising direction for early diagnosis and prognosis of the course of metabolic dysfunction-associated fatty liver disease, while the study of molecular components of DNA methylation mechanisms involved in the regulation of gene expression, the dependence of their activity on exposure to the exposome will allow to personalize and improve recommendations for lifestyle and diet modification in patients with metabolic dysfunction-associated fatty liver disease.