Cross-Kingdom DNA Methylation Dynamics: Comparative Mechanisms of 5mC/6mA Regulation and Their Implications in Epigenetic Disorders

• Published in: Biology (Basel, Switzerland) Vol. 14; no. 5; p. 461
• Main Authors: Liu, Yu, Wang, Ying, Bao, Dapeng, Chen, Hongyu, Gong, Ming, Sun, Shujing, Zou, Gen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 24.04.2025; MDPI
• Subjects: 5mC; 6mA; B cells; Binding sites; chromatin architecture; Chromatin remodeling; Comparative analysis; CRISPR; Demethylation; Developmental stages; DNA; DNA methylation; Enzymes; Epigenetic inheritance; epigenetic regulation; Epigenetics; Evolutionary conservation; Gene expression; Genomes; Genomic imprinting; Genomics; Liu, Timothy; Methylation; N6-methyladenosine; Neurodegenerative diseases; Proteins; Review; RNA polymerase; Transcription factors; Tumorigenesis; Wildlife conservation; DNA methylation; chromatin architecture; 6mA; 5mC; epigenetic regulation
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology14050461

DNA methylation, a cornerstone of epigenetic regulation, governs critical biological processes including transcriptional modulation, genomic imprinting, and transposon suppression through chromatin architecture remodeling. Recent advances have revealed that aberrant methylation patterns—characterized by spatial-temporal dysregulation and stochastic molecular noise—serve as key drivers of diverse pathological conditions, from oncogenesis to neurodegenerative disorders. However, the field faces dual challenges: (1) current understanding remains fragmented due to the inherent spatiotemporal heterogeneity of methylation landscapes across tissues and developmental stages, and (2) mechanistic insights into non-canonical methylation pathways (particularly 6mA) in non-mammalian systems are conspicuously underdeveloped. This review systematically synthesizes the evolutionary-conserved versus species-specific features of 5-methylcytosine (5mC) and N6-methyladenine (6mA) regulatory networks across three biological kingdoms. Through comparative analysis of methylation/demethylation enzymatic cascades (DNMTs/TETs in mammals, CMTs/ROS1 in plants, and DIM-2/DNMTA in fungi), we propose a unified framework for targeting methylation-associated diseases through precision epigenome editing, while identifying critical knowledge gaps in fungal methylome engineering that demand urgent investigation.