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Role of m6A mRNA Methylation in Plant Defense. m6A mRNA甲基化在植物防御中的作用。
IF 3.5
Epigenomes Pub Date : 2025-10-15 DOI: 10.3390/epigenomes9040042
Rakesh Srivastava, Niraj Lodhi
{"title":"Role of m<sup>6</sup>A mRNA Methylation in Plant Defense.","authors":"Rakesh Srivastava, Niraj Lodhi","doi":"10.3390/epigenomes9040042","DOIUrl":"10.3390/epigenomes9040042","url":null,"abstract":"<p><p>N6-methyladenosine (m<sup>6</sup>A) is the most abundant and dynamic RNA modification in eukaryotic messenger and non-coding RNAs, playing a pivotal role in the post-transcriptional regulation of gene expression. The coordinated actions of m<sup>6</sup>A writers, erasers, and readers influence transcript stability, immune activation, and pathogen suppression. Growing evidence indicates that m<sup>6</sup>A fine-tunes the expression of defense-related genes, modulates RNA processing events, and is frequently hijacked by pathogens and pests to promote virulence. Notably, the dual role of m<sup>6</sup>A in enhancing plant defense and facilitating pathogen adaptation highlights its significance in the host-pathogen arms race. This review emphasizes recent advances in our understanding of m<sup>6</sup>A-mediated epitranscriptomic regulation in plants, with a focus on its role in responses to biotic stresses, including fungi, bacteria, virus infections, insects, and nematode attacks. This regulatory layer offers novel opportunities for crop protection through targeted manipulation of the epitranscriptomic mechanism.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12550991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated Alcohol Consumption and Chronic Inflammation Predict Cardiovascular Risk Among Black Americans: Examination of a Dual-Risk Model Using Epigenetic Risk Markers. 饮酒增加和慢性炎症预测美国黑人心血管风险:使用表观遗传风险标记的双风险模型检验
IF 3.5
Epigenomes Pub Date : 2025-10-07 DOI: 10.3390/epigenomes9040040
Steven R H Beach, Robert A Philibert, Mei-Ling Ong, Man-Kit Lei, Kaixiong Ye
{"title":"Elevated Alcohol Consumption and Chronic Inflammation Predict Cardiovascular Risk Among Black Americans: Examination of a Dual-Risk Model Using Epigenetic Risk Markers.","authors":"Steven R H Beach, Robert A Philibert, Mei-Ling Ong, Man-Kit Lei, Kaixiong Ye","doi":"10.3390/epigenomes9040040","DOIUrl":"10.3390/epigenomes9040040","url":null,"abstract":"<p><strong>Background: </strong>Heart disease may take a greater toll on Black Americans than White Americans despite similar levels of traditional risk factors. Elevated alcohol consumption (EAC) and chronic inflammation are two potentially important additional risk factors to consider. Both are relevant to understanding health disparities in cardiovascular health.</p><p><strong>Methods: </strong>Couples with a Black preadolescent or early adolescent child living in the home were recruited and followed. In waves 5 and 6 of data collection, biological samples were also collected allowing the characterization of elevated alcohol consumption, chronic inflammation, and cardiac risk using DNA methylation indices. 383 individual partners comprising 221 couples were examined across the two waves of data, yielding 661 person-wave observations from 383 individuals.</p><p><strong>Results: </strong>EAC at wave 5 forecast increased cardiac risk at W6 (R<sup>2</sup> change = 0.276), β = -0.193, <i>p</i> = 0.001. However, chronic inflammation at wave 5 did not add significantly to the baseline model, β = -0.042, <i>p</i> = 0.549. Conversely, the slope of change for chronic inflammation was associated with slope of change in cardiac risk (R<sup>2</sup> change = 0.111), b = -0.014, <i>p</i> = <0.001, but EAC change was not significantly associated with change in cardiac risk, b = -0.001, <i>p</i> = 0.185.</p><p><strong>Conclusions: </strong>Elevated alcohol consumption may be an important risk factor for increased cardiac risk over time in middle age. If so, it could be an important avenue for preventative intervention to decrease cardiac risk. Future research should examine whether similar associations are observed for other racial or minoritized groups and for non-minoritized groups.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Pilot Epigenome-Wide Study of Posttraumatic Growth: Identifying Novel Candidates for Future Research. 创伤后生长的试点全表观基因组研究:确定未来研究的新候选人。
IF 3.5
Epigenomes Pub Date : 2025-10-06 DOI: 10.3390/epigenomes9040039
Mackenzie Rubens, Paul Ruiz Pinto, Anita Sathyanarayanan, Olivia Miller, Amy B Mullens, Dagmar Bruenig, Patricia Obst, Jane Shakespeare-Finch, Divya Mehta
{"title":"A Pilot Epigenome-Wide Study of Posttraumatic Growth: Identifying Novel Candidates for Future Research.","authors":"Mackenzie Rubens, Paul Ruiz Pinto, Anita Sathyanarayanan, Olivia Miller, Amy B Mullens, Dagmar Bruenig, Patricia Obst, Jane Shakespeare-Finch, Divya Mehta","doi":"10.3390/epigenomes9040039","DOIUrl":"10.3390/epigenomes9040039","url":null,"abstract":"<p><strong>Background: </strong>Posttraumatic growth (PTG) refers to positive psychological change following trauma. While its psychological aspects are well-documented, the biological mechanisms remain unclear. Epigenetic changes, such as DNA methylation (DNAm), may offer insight into PTG's neurobiological basis.</p><p><strong>Aims: </strong>This study aimed to identify epigenetic markers associated with PTG using an epigenome-wide association study (EWAS), the first of its kind in a trauma-exposed population.</p><p><strong>Methods: </strong>A longitudinal EWAS design was used to assess DNAm before and after trauma exposure in first-year paramedicine students (n = 39). Genome-wide methylation data were analyzed for associations with PTG, applying epigenome-wide and gene-wise statistical thresholds. Pathway enrichment analysis was also conducted.</p><p><strong>Results: </strong>The study identified two CpGs (cg09559117 and cg05351447) within the PCDHA1/PCDHA2 and PDZD genes significantly associated with PTG at the epigenome-wide threshold (<i>p</i> < 9.42 × 10<sup>-8</sup>); these were replicated in an independent sample. DNAm in 5 CpGs across known PTSD candidate genes ANK3, DICER1, SKA2, IL12B and TPH1 were significantly associated with PTG after gene-wise Bonferroni correction. Pathway analysis revealed that PTG-associated genes were overrepresented in the Adenosine triphosphate Binding Cassette (ABC) transporters pathway (<i>p</i> = 2.72 × 10<sup>-4</sup>).</p><p><strong>Conclusions: </strong>These results identify genes for PTG, improving our understanding of the neurobiological underpinnings of PTG.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tripartite Interaction of Epigenetic Regulation, Brain Aging, and Neuroinflammation: Mechanistic Insights and Therapeutic Implications. 表观遗传调控、脑衰老和神经炎症的三方相互作用:机制见解和治疗意义。
IF 3.5
Epigenomes Pub Date : 2025-10-05 DOI: 10.3390/epigenomes9040038
Shenghui Mi, Hideyuki Nakashima, Kinichi Nakashima
{"title":"Tripartite Interaction of Epigenetic Regulation, Brain Aging, and Neuroinflammation: Mechanistic Insights and Therapeutic Implications.","authors":"Shenghui Mi, Hideyuki Nakashima, Kinichi Nakashima","doi":"10.3390/epigenomes9040038","DOIUrl":"10.3390/epigenomes9040038","url":null,"abstract":"<p><p>Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms-such as DNA methylation and histone modification-in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sustained Higher Levels of Plasma hsa-miR-17-5p Expression During Gestational Diabetes Mellitus and Postpartum. 妊娠期糖尿病和产后血浆hsa-miR-17-5p表达持续升高
IF 3.5
Epigenomes Pub Date : 2025-09-24 DOI: 10.3390/epigenomes9040037
Arathi Pillai, Sibin M Kandi, Nidhi Tripathy, Deeptika Agarwal, Indrani Mukhopadhyay, Bhasker Mukherjee, Y Vashum
{"title":"Sustained Higher Levels of Plasma hsa-miR-17-5p Expression During Gestational Diabetes Mellitus and Postpartum.","authors":"Arathi Pillai, Sibin M Kandi, Nidhi Tripathy, Deeptika Agarwal, Indrani Mukhopadhyay, Bhasker Mukherjee, Y Vashum","doi":"10.3390/epigenomes9040037","DOIUrl":"10.3390/epigenomes9040037","url":null,"abstract":"<p><p><b>Background:</b> The role of circulatory miRNAs in gestational diabetes mellitus (GDM) was explored extensively in previous studies. However, there was limited literature on longitudinal studies exploring the changes in miRNA expression during pregnancy and postpartum to understand the changes in their expression levels in GDM patients. <b>Methods:</b> Blood samples from thirty GDM subjects and twenty normoglycemic pregnant women (NGT) were collected between 24 and 28 weeks of their pregnancy, and follow-up samples from the same subjects were collected till 12 weeks postpartum (FGDM and FNGT, respectively). Three candidate miRNAs, hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p, were quantified from their plasma samples using RT-qPCR. Comparative analysis of these miRNA expression levels was made between different groups. <b>Results:</b> hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p expression were significantly higher in GDM patients when compared to NGT subjects. Interestingly, hsa-miR-17-5p has shown consistent upregulation in FGDM even after these patients turned normoglycemic. Additionally, hsa-miR-16-5p was found to be higher in FGDM patients compared to FNGT subjects. <b>Conclusions:</b> The present study corroborated the finding of differential expression of hsa-miR-16-5p, hsa-miR-17-5p, and hsa-miR-20a-5p in GDM. It also marked the importance of monitoring the levels of hsa-miR-17-5p and hsa-miR-16-5p during pregnancy and postpartum in GDM patients.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 4","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
m6A RNA Methylation in Psychiatric Disorders: An Emerging Epitranscriptomic Axis. 精神疾病中的m6A RNA甲基化:一个新兴的表转录组轴。
IF 3.5
Epigenomes Pub Date : 2025-09-19 DOI: 10.3390/epigenomes9030036
Ambrose Loc Ngo, Linda Nguyen, Niki Gharavi Alkhansari, Huiping Zhang
{"title":"m<sup>6</sup>A RNA Methylation in Psychiatric Disorders: An Emerging Epitranscriptomic Axis.","authors":"Ambrose Loc Ngo, Linda Nguyen, Niki Gharavi Alkhansari, Huiping Zhang","doi":"10.3390/epigenomes9030036","DOIUrl":"10.3390/epigenomes9030036","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is the most prevalent internal modification in eukaryotic messenger RNA (mRNA) and plays a vital role in post-transcriptional gene regulation. In recent years, m<sup>6</sup>A has emerged as a pivotal epitranscriptomic signal involved in neural development, synaptic remodeling, and the molecular pathophysiology of neuropsychiatric disorders. In this review, we summarize the mechanisms underlying the deposition, removal, and recognition of m<sup>6</sup>A by dedicated methyltransferases, demethylases, and RNA-binding proteins. We further explore how these dynamic modifications influence neuronal differentiation and memory formation. Recent studies have linked aberrant m<sup>6</sup>A regulation to psychiatric conditions such as depression, anxiety, schizophrenia, and bipolar disorder. Additionally, we discuss how pharmacological or genetic modulation of m<sup>6</sup>A pathways may promote adaptive neural plasticity and enhance cognitive and emotional resilience. Despite these promising findings, significant challenges remain in achieving spatial and temporal specificity while minimizing off-target effects in the brain. Therefore, we advocate for more in-depth investigations into m<sup>6</sup>A function within developmentally defined neural circuits to better understand its enduring role in maintaining neural homeostasis.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Mapping of N6-Methyladenine, C5-Methylcytosine, and C5-Hydroxymethylcytosine in a Single Species Reveals Constitutive, Somatic- and Germline-Specific, and Age-Related Genomic Context Distributions and Biological Functions. 单个物种中n6 -甲基腺嘌呤、c5 -甲基胞嘧啶和c5 -羟甲基胞嘧啶的比较定位揭示了构成、体细胞和种系特异性、年龄相关的基因组背景分布和生物学功能。
IF 4.1
Epigenomes Pub Date : 2025-09-18 DOI: 10.3390/epigenomes9030035
Thibaut Renard, Serge Aron
{"title":"Comparative Mapping of N6-Methyladenine, C5-Methylcytosine, and C5-Hydroxymethylcytosine in a Single Species Reveals Constitutive, Somatic- and Germline-Specific, and Age-Related Genomic Context Distributions and Biological Functions.","authors":"Thibaut Renard, Serge Aron","doi":"10.3390/epigenomes9030035","DOIUrl":"10.3390/epigenomes9030035","url":null,"abstract":"<p><strong>Background/objectives: </strong>The DNA methylome allows environmental signals to be converted into stable and adaptive changes in gene expression. While 5-methylcytosine (5mC) has been extensively studied, alternative epigenetic marks such as N6-methyladenine (6mA) and 5-hydroxymethylcytosine (5hmC) remain poorly understood. Comparative studies of these marks are rare, and their results are often confounded by phylogeny, tissue type, developmental stage, or methodology. Here, we aimed to disentangle the constitutive, somatic- and germline-specific, and/or age-related patterns displayed by 6mA, 5mC, and 5hmC within a single species.</p><p><strong>Methods: </strong>We generated long-read nanopore sequencing data for somatic tissues of buff-tailed bumblebee (<i>Bombus terrestris</i>) males and their sperm, enabling simultaneous detection of 6mA, 5mC, and 5hmC. We used a stepwise approach to successively identify (i) constitutive patterns conserved between somatic tissues and sperm, (ii) differences between the soma and the germline, and (iii) age-related changes between young and old males.</p><p><strong>Results: </strong>We found distinct constitutive, somatic and sperm, and age-related specific signatures in the genomic contexts, maintenance fidelity, and biological functions associated with 6mA, 5mC, and 5hmC. Sperm cells consistently displayed lower methylation entropy than did somatic tissues, indicating more stable methylation patterns in the germline. 5mC exhibited the greatest variation across all genomic contexts; 6mA and 5hmC displayed less dramatic differences. The influence of age was subtler but revealed context-dependent remodeling of methylation, particularly for 5hmC.</p><p><strong>Conclusions: </strong>We observed that 6mA, 5mC, and 5hmC displayed constitutive, somatic- and sperm-specific, and age-related differences that were associated with distinct genomic contexts and biological functions, supporting the complementarity of these methylation marks and their diverging epigenetic roles.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Deciphering the Heterogeneity of Pancreatic Cancer: DNA Methylation-Based Cell Type Deconvolution Unveils Distinct Subgroups and Immune Landscapes. 解读胰腺癌的异质性:基于DNA甲基化的细胞类型反卷积揭示了不同的亚群和免疫景观。
IF 3.5
Epigenomes Pub Date : 2025-09-05 DOI: 10.3390/epigenomes9030034
Barbara Mitsuyasu Barbosa, Alexandre Todorovic Fabro, Roberto da Silva Gomes, Claudia Aparecida Rainho
{"title":"Deciphering the Heterogeneity of Pancreatic Cancer: DNA Methylation-Based Cell Type Deconvolution Unveils Distinct Subgroups and Immune Landscapes.","authors":"Barbara Mitsuyasu Barbosa, Alexandre Todorovic Fabro, Roberto da Silva Gomes, Claudia Aparecida Rainho","doi":"10.3390/epigenomes9030034","DOIUrl":"10.3390/epigenomes9030034","url":null,"abstract":"<p><p><b>Background:</b> Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy, characterized by low tumor cellularity, a dense stromal response, and intricate cellular and molecular interactions within the tumor microenvironment (TME). Although bulk omics technologies have enhanced our understanding of the molecular landscape of PDAC, the specific contributions of non-malignant immune and stromal components to tumor progression and therapeutic response remain poorly understood. <b>Methods:</b> We explored genome-wide DNA methylation and transcriptomic data from the Cancer Genome Atlas Pancreatic Adenocarcinoma cohort (TCGA-PAAD) to profile the immune composition of the TME and uncover gene co-expression networks. Bioinformatic analyses included DNA methylation profiling followed by hierarchical deconvolution, epigenetic age estimation, and a weighted gene co-expression network analysis (WGCNA). <b>Results:</b> The unsupervised clustering of methylation profiles identified two major tumor groups, with Group 2 (n = 98) exhibiting higher tumor purity and a greater frequency of <i>KRAS</i> mutations compared to Group 1 (n = 87) (<i>p</i> < 0.0001). The hierarchical deconvolution of DNA methylation data revealed three distinct TME subtypes, termed hypo-inflamed (immune-deserted), myeloid-enriched, and lymphoid-enriched (notably T-cell predominant). These immune clusters were further supported by co-expression modules identified via WGCNA, which were enriched in immune regulatory and signaling pathways. <b>Conclusions:</b> This integrative epigenomic-transcriptomic analysis offers a robust framework for stratifying PDAC patients based on the tumor immune microenvironment (TIME), providing valuable insights for biomarker discovery and the development of precision immunotherapies.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innate Immune Surveillance and Recognition of Epigenetic Marks. 表观遗传标记的先天免疫监视和识别。
IF 3.5
Epigenomes Pub Date : 2025-09-05 DOI: 10.3390/epigenomes9030033
Yalong Wang
{"title":"Innate Immune Surveillance and Recognition of Epigenetic Marks.","authors":"Yalong Wang","doi":"10.3390/epigenomes9030033","DOIUrl":"10.3390/epigenomes9030033","url":null,"abstract":"<p><p>The innate immune system protects against infection and cellular damage by recognizing conserved pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Emerging evidence suggests that aberrant epigenetic modifications-such as altered DNA methylation and histone marks-can serve as immunogenic signals that activate pattern recognition receptor (PRR)-mediated immune surveillance. This review explores the concept that epigenetic marks may function as DAMPs or even mimic PAMPs. I highlight how unmethylated CpG motifs, which are typically suppressed using host methylation, are recognized as foreign via Toll-like receptor 9 (TLR9). I also examine how cytosolic DNA sensors, including cGAS, detect mislocalized or hypomethylated self-DNA resulting from genomic instability. In addition, I discuss how extracellular histones and nucleosomes released during cell death or stress can act as DAMPs that engage TLRs and activate inflammasomes. In the context of cancer, I review how epigenetic dysregulation can induce a \"viral mimicry\" state, where reactivation of endogenous retroelements produces double-stranded RNA sensed by RIG-I and MDA5, triggering type I interferon responses. Finally, I address open questions and future directions, including how immune recognition of epigenetic alterations might be leveraged for cancer immunotherapy or regulated to prevent autoimmunity. By integrating recent findings, this review underscores the emerging concept of the epigenome as a target of innate immune recognition, bridging the fields of immunology, epigenetics, and cancer biology.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Epigenomic Meta-Analysis of Differentially Methylated Sites in Pre- and Post-Metabolic/Bariatric Surgery Adult Female Patients. 代谢/减肥手术前后成年女性患者甲基化位点差异的表观基因组meta分析
IF 3.5
Epigenomes Pub Date : 2025-08-29 DOI: 10.3390/epigenomes9030032
Agnieszka Lovett, Graham A Hitman, Georgios K Dimitriadis, Alice M Murphy, Gyanendra Tripathi, Aparna Duggirala
{"title":"An Epigenomic Meta-Analysis of Differentially Methylated Sites in Pre- and Post-Metabolic/Bariatric Surgery Adult Female Patients.","authors":"Agnieszka Lovett, Graham A Hitman, Georgios K Dimitriadis, Alice M Murphy, Gyanendra Tripathi, Aparna Duggirala","doi":"10.3390/epigenomes9030032","DOIUrl":"10.3390/epigenomes9030032","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metabolic/bariatric surgery is currently the most successful treatment for patients with obesity; however, a fifth of patients undergoing surgery may not lose enough weight to be considered successful. Recent studies have shown that bariatric/metabolic surgery alters the epigenome and may explain postoperative improvements in metabolic health. The primary objective is to consolidate published differentially methylated CpG sites in pre- and post-metabolic/bariatric surgery female patients and associate them with the respective genes and pathways.</p><p><strong>Methods: </strong>This systematic review adhered to the PRISMA-P guidelines and was registered with the PROSPERO (CRD42023421852). Following an initial screening of 541 studies using COVIDENCE, six studies were selected, comprising three epigenome-wide association studies (EWAS) and three candidate gene methylation studies. The published studies collected DNA samples from female patients with obesity before and after surgery (3 months, 6 months, 9-31 months, and 2 years). KEGG pathway analysis was performed on genes where the extracted CpG sites were located.</p><p><strong>Results: </strong>The meta-analysis showed that 11,456 CpG sites are differentially methylated after a successful weight loss surgery, with 109 sites mapped to genes involved in key metabolic pathways, including FoxO, mTOR, insulin, cAMP, adipocytokine, Toll-like receptor, and PI3K-Akt.</p><p><strong>Conclusion: </strong>The highlighted differentially methylated CpG sites can be further used to predict the molecular signature associated with successful metabolic/bariatric surgery.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12452392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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