{"title":"表观遗传网络协调整个基因组的DNA甲基化","authors":"Wolfgang Wagner","doi":"10.1016/j.ymthe.2025.06.037","DOIUrl":null,"url":null,"abstract":"The epigenetic landscape governs cell-fate decisions during development, aging, and disease. Despite considerable progress in understanding of DNA methylation (DNAm), the mechanisms that orchestrate its coordinated regulation across the genome remain largely elusive. Recent breakthroughs in sequencing technologies and epigenetic editing tools enable more comprehensive exploration of these epigenetic interactions. Regulation of DNAm seems to be organized within epigenetic networks characterized by complex feedback mechanisms acting locally, between homologous alleles, and across the entire genome. This crosstalk is facilitated by an interplay of various molecular components, including distinct variants of epigenetic writers and erasers; methylation-sensitive binding of transcription factors and other regulatory proteins that recruit DNA methyltransferases; cross-regulation between DNAm and the histone code; 3D chromatin conformation; regulatory effects mediated by long non-coding RNAs (lncRNAs); and potentially by assimilation during homologous recombination events. This review explores how these diverse epigenetic mechanisms interact to collectively shape the methylome, and thereby control developmental and disease processes.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"11 1","pages":""},"PeriodicalIF":12.1000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Epigenetic networks coordinate DNA methylation across the genome\",\"authors\":\"Wolfgang Wagner\",\"doi\":\"10.1016/j.ymthe.2025.06.037\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The epigenetic landscape governs cell-fate decisions during development, aging, and disease. Despite considerable progress in understanding of DNA methylation (DNAm), the mechanisms that orchestrate its coordinated regulation across the genome remain largely elusive. Recent breakthroughs in sequencing technologies and epigenetic editing tools enable more comprehensive exploration of these epigenetic interactions. Regulation of DNAm seems to be organized within epigenetic networks characterized by complex feedback mechanisms acting locally, between homologous alleles, and across the entire genome. This crosstalk is facilitated by an interplay of various molecular components, including distinct variants of epigenetic writers and erasers; methylation-sensitive binding of transcription factors and other regulatory proteins that recruit DNA methyltransferases; cross-regulation between DNAm and the histone code; 3D chromatin conformation; regulatory effects mediated by long non-coding RNAs (lncRNAs); and potentially by assimilation during homologous recombination events. This review explores how these diverse epigenetic mechanisms interact to collectively shape the methylome, and thereby control developmental and disease processes.\",\"PeriodicalId\":19020,\"journal\":{\"name\":\"Molecular Therapy\",\"volume\":\"11 1\",\"pages\":\"\"},\"PeriodicalIF\":12.1000,\"publicationDate\":\"2025-06-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ymthe.2025.06.037\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.06.037","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
Epigenetic networks coordinate DNA methylation across the genome
The epigenetic landscape governs cell-fate decisions during development, aging, and disease. Despite considerable progress in understanding of DNA methylation (DNAm), the mechanisms that orchestrate its coordinated regulation across the genome remain largely elusive. Recent breakthroughs in sequencing technologies and epigenetic editing tools enable more comprehensive exploration of these epigenetic interactions. Regulation of DNAm seems to be organized within epigenetic networks characterized by complex feedback mechanisms acting locally, between homologous alleles, and across the entire genome. This crosstalk is facilitated by an interplay of various molecular components, including distinct variants of epigenetic writers and erasers; methylation-sensitive binding of transcription factors and other regulatory proteins that recruit DNA methyltransferases; cross-regulation between DNAm and the histone code; 3D chromatin conformation; regulatory effects mediated by long non-coding RNAs (lncRNAs); and potentially by assimilation during homologous recombination events. This review explores how these diverse epigenetic mechanisms interact to collectively shape the methylome, and thereby control developmental and disease processes.
期刊介绍:
Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.