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

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—characterize...

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Published inBiology (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
LanguageEnglish
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
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Abstract 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.
AbstractList DNA methylation regulates gene expression and genome stability. Challenges include tissue-specific spatiotemporal heterogeneity and poorly understood non-canonical 6mA pathways. This review compares conserved vs. species-specific 5mC/6mA networks across animals, plants, and fungi by analyzing enzymes (DNMTs/TETs, CMTs/ROS1, DIM-2/DNMTAs), proposing precision epigenome editing for therapies. Critical gaps persist in fungal methylome engineering, urging mechanistic studies to harness evolutionary insights for biotechnological and biomedical advances. 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.
DNA methylation regulates gene expression and genome stability. Challenges include tissue-specific spatiotemporal heterogeneity and poorly understood non-canonical 6mA pathways. This review compares conserved vs. species-specific 5mC/6mA networks across animals, plants, and fungi by analyzing enzymes (DNMTs/TETs, CMTs/ROS1, DIM-2/DNMTAs), proposing precision epigenome editing for therapies. Critical gaps persist in fungal methylome engineering, urging mechanistic studies to harness evolutionary insights for biotechnological and biomedical advances.
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.
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.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.
Audience Academic
Author Gong, Ming
Liu, Yu
Wang, Ying
Bao, Dapeng
Zou, Gen
Sun, Shujing
Chen, Hongyu
AuthorAffiliation 2 National Engineering Research Center of Edible Fungi, Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Rd., Shanghai 201403, China; wyhrx@126.com (Y.W.); baodapeng@saas.sh.cn (D.B.)
1 College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
AuthorAffiliation_xml – name: 1 College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
– name: 2 National Engineering Research Center of Edible Fungi, Institute of Edible Fungi, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Rd., Shanghai 201403, China; wyhrx@126.com (Y.W.); baodapeng@saas.sh.cn (D.B.)
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Keywords DNA methylation
chromatin architecture
6mA
5mC
epigenetic regulation
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RelatedPersons Liu, Timothy
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Snippet DNA methylation, a cornerstone of epigenetic regulation, governs critical biological processes including transcriptional modulation, genomic imprinting, and...
DNA methylation regulates gene expression and genome stability. Challenges include tissue-specific spatiotemporal heterogeneity and poorly understood...
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SubjectTerms 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
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Title Cross-Kingdom DNA Methylation Dynamics: Comparative Mechanisms of 5mC/6mA Regulation and Their Implications in Epigenetic Disorders
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Volume 14
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