EpigenomicsPub Date : 2025-05-27DOI: 10.1080/17501911.2025.2510196
Wu Duan, Ziyi Peng, Kun Yang, Mengyuan Hu, Xuefeng Yu, Benping Zhang, Li Liu
{"title":"Transcriptome-wide N6-methyladenosine methylation dynamic profile in type 1 diabetes progression.","authors":"Wu Duan, Ziyi Peng, Kun Yang, Mengyuan Hu, Xuefeng Yu, Benping Zhang, Li Liu","doi":"10.1080/17501911.2025.2510196","DOIUrl":"https://doi.org/10.1080/17501911.2025.2510196","url":null,"abstract":"<p><strong>Aims: </strong>To map transcriptome-wide N6-methyladenosine (m6A) profile at different stages of type 1 diabetes (T1D).</p><p><strong>Materials & methods: </strong>RNA extracted from islet tissues of non-obese diabetic mice at different ages (4-week-old control group, 8-week-old pre-diabetes group, and 14-week-old diabetes group) was analyzed by MeRIP-seq and mRNA-seq. Bioinformatics analyses, including m6A motif enrichment, differential methylation, gene ontology and pathway analysis.</p><p><strong>Results: </strong>Bioinformatic analysis revealed a progressive increase in m6A methylation sites and unique peaks throughout diabetes progression. The predominant m6A motif was \"GGACU\" in the control and pre-diabetes stages, shifting to \"GGACU/A\" in the diabetes stage. m6A modifications were primarily enriched at the start codon, coding region, and stop codon. Integrated analysis found pre-diabetes, diabetes groups showed distinct m6A and mRNA changes versus control. Pathway analysis indicated that differentially expressed mRNAs with m6A methylation were predominantly enriched in insulin/IGF-MAPKK/MAPK cascades, apoptosis, T-cell activation, interleukins, CCKR, and inflammation-related pathways in the pre-diabetes stage. As diabetes progressed, additional pathways, including Wnt, EGF receptor, PDGF, GnRH receptor, and angiogenesis, became involved in disease development. In vitro, cytokine stimulation of INS-1 cells increased m6A methylation, upregulated METTL3, downregulated ALKBH5.</p><p><strong>Conclusions: </strong>m6A methyl group dynamics in T1D disease progression, potentially influencing mRNA expression and signal transduction pathways.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-25DOI: 10.1080/17501911.2025.2510190
Suvo Chatterjee, Jing Wu, Marion Ouidir, Katherine L Grantz, Fasil Tekola-Ayele
{"title":"Association of placental weight and placental-fetal weight ratio with DNA methylation in placenta.","authors":"Suvo Chatterjee, Jing Wu, Marion Ouidir, Katherine L Grantz, Fasil Tekola-Ayele","doi":"10.1080/17501911.2025.2510190","DOIUrl":"https://doi.org/10.1080/17501911.2025.2510190","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the association between placental methylation and placenta weight (PW) and placental-fetal weight ratio (PFR), which are markers of placental function linked to adverse pregnancy outcomes and risk for diseases in later life.</p><p><strong>Methods: </strong>We examined the association between placental epigenome-wide methylation and PW and PFR at birth (<i>n</i> = 301). Further tests assessed whether methylation levels of the cytosine-guanine sites (CpGs) linked to PW and PFR are associated with placental expression of nearby genes.</p><p><strong>Results: </strong>At a 5% false discovery rate (FDR), methylation at 27 CpGs was associated with PW, of which two CpGs were also associated with PFR. Methylation at four of the 27 CpGs was associated with placental expression of nearby genes including LEPR, RPS6KA1, and COX5A which have known roles in early development, cellular growth, and oxidative stress. The identified CpGs overlap with previously reported methylation sites associated with perinatal and adult health outcomes such as preeclampsia, preterm delivery, obesity, and type 2 diabetes.</p><p><strong>Conclusions: </strong>The findings reveal epigenetic underpinnings of placental development and functional efficiency, and suggest their potential roles in mediating fetal development and late-onset diseases.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-10"},"PeriodicalIF":3.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-16DOI: 10.1080/17501911.2025.2504333
Michael S Bosmeny, Joao I Mamede, Keith T Gagnon
{"title":"Resolving sequencing-based HIV-1 epitranscriptomics.","authors":"Michael S Bosmeny, Joao I Mamede, Keith T Gagnon","doi":"10.1080/17501911.2025.2504333","DOIUrl":"https://doi.org/10.1080/17501911.2025.2504333","url":null,"abstract":"<p><p>The collection of HIV-1 RNA chemical modifications and their functional consequences in viral gene expression, host interactions, and the viral life cycle, referred to as HIV-1 epitranscriptomics, remain incompletely understood. While the field is evolving, diverse modification discovery methods, cell lines, HIV-1 sequences, and bioinformatics methods make a consensus view of the HIV-1 epitranscriptome difficult to resolve. Here, we review methods for identifying and interpreting N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), 5-methylcytosine (m<sup>5</sup>C), pseudouridine (Ψ), 2´-<i>O</i>-methylation (N<sub>m</sub>), and N<sup>4</sup>-acetylcytidine (ac<sup>4</sup>C) modifications in HIV-1, including antibody-based selection methods, chemical-treatment-based selection methods, and detection by nanopore direct RNA sequencing. We recommend the adoption of the latter as a standardized sequencing strategy to enable better benchmarking across diverse studies and help resolve HIV-1 epitranscriptomics.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-10DOI: 10.1080/17501911.2025.2500907
Paraskevi Christofidou, Christopher G Bell
{"title":"The predictive power of profiling the DNA methylome in human health and disease.","authors":"Paraskevi Christofidou, Christopher G Bell","doi":"10.1080/17501911.2025.2500907","DOIUrl":"https://doi.org/10.1080/17501911.2025.2500907","url":null,"abstract":"<p><p>Early and accurate diagnosis significantly improves the chances of disease survival. DNA methylation (5mC), the major DNA modification in the human genome, is now recognized as a biomarker of immense clinical potential. This is due to its ability to delineate precisely cell-type, quantitate both internal and external exposures, as well as tracking chronological and biological components of the aging process. Here, we survey the current state of DNA methylation as a biomarker and predictor of traits and disease. This includes Epigenome-wide association study (EWAS) findings that inform Methylation Risk Scores (MRS), EpiScore long-term estimators of plasma protein levels, and machine learning (ML) derived DNA methylation clocks. These all highlight the significant benefits of accessible peripheral blood DNA methylation as a surrogate measure. However, detailed DNA methylation biopsy analysis in real-time is also empowering pathological diagnosis. Furthermore, moving forward, in this multi-omic and biobank scale era, novel insights will be enabled by the amplified power of increasing sample sizes and data integration.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-12"},"PeriodicalIF":3.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-08DOI: 10.1080/17501911.2025.2501524
Srija Roy, Mrinal K Ghosh
{"title":"Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer.","authors":"Srija Roy, Mrinal K Ghosh","doi":"10.1080/17501911.2025.2501524","DOIUrl":"https://doi.org/10.1080/17501911.2025.2501524","url":null,"abstract":"<p><p>The ubiquitin proteasome system (UPS), comprising of ubiquitinases, deubiquitinases and 26S proteasome plays a significant role in directly or indirectly regulating epigenetic players. DNA-templated processes like replication, repair and transcription require chromatin decondensation to allow access to specific DNA sequence. A thorough survey of literary articles in PubMed database revealed that the UPS functions as a key regulator, determining the precise state of open and closed chromatin by influencing histones and histone modifiers through proteolytic or non-proteolytic means. However, a comprehensive understanding of how specific UPS components affect particular epigenetic pathways in response to environmental cues remains underexplored. This axis holds substantial potential for deciphering mechanisms of tumorigenesis. Although our current knowledge is limited, it can still guide the development of novel therapeutic strategies that can potentially bridge the gap between cancer chemotherapeutics in bench and bedside.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-20"},"PeriodicalIF":3.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-06DOI: 10.1080/17501911.2025.2500914
Vaidotas Stankevičius, Liepa Gasiulė, Giedrius Vilkaitis, Saulius Klimašauskas
{"title":"Selective chemical tracking of DNA methylomes in live cells.","authors":"Vaidotas Stankevičius, Liepa Gasiulė, Giedrius Vilkaitis, Saulius Klimašauskas","doi":"10.1080/17501911.2025.2500914","DOIUrl":"https://doi.org/10.1080/17501911.2025.2500914","url":null,"abstract":"","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-3"},"PeriodicalIF":3.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulatory roles of transposable elements on autism molecular neuropathology.","authors":"Peerapa Techaniyom, Chawin Korsirikoon, Pitaksin Chitta, Chanachai Sae-Lee","doi":"10.1080/17501911.2025.2501520","DOIUrl":"https://doi.org/10.1080/17501911.2025.2501520","url":null,"abstract":"<p><p>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by challenges in social communication and the presence of repetitive behaviors, typically diagnosed in early childhood. In this review, we searched PubMed and Google Scholar databases for relevant articles. ASD displays considerable heterogeneity in symptomatology and is more common in males, though shifting demographics indicate rising rates among minority populations. Transposable elements (TEs), which constitute approximately 50% of the mammalian genome, are increasingly recognized for their contribution to neurodevelopmental disorders, including ASD. These mobile genetic elements can induce genomic instability and modulate gene expression, thereby influencing ASD pathology. Evidence suggests that specific TEs, such as L1 and <i>Alu</i> elements, can disrupt genes critical for neurodevelopment and contribute to the disorder's genetic complexity. Furthermore, prenatal environmental exposures may activate TEs, potentially contributing to neuroinflammation observed in ASD. While the precise regulatory roles of non-coding TEs in ASD are still under investigation and require careful interpretation, integrating epigenetic aging markers like epigenetic clocks holds promise for advancing the field. Future research focused on the intricate relationship between TEs, environmental factors, epigenetic mechanisms, and neurodevelopmental processes is essential for identifying novel biomarkers and therapeutic targets, ultimately improving early diagnosis and interventions for ASD.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"1-9"},"PeriodicalIF":3.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-01Epub Date: 2025-03-14DOI: 10.1080/17501911.2025.2476380
Abudurousuli Reyila, Xianchun Gao, Jun Yu, Yongzhan Nie
{"title":"Insight into the role of DNA methylation in prognosis and treatment response prediction of gastrointestinal cancers.","authors":"Abudurousuli Reyila, Xianchun Gao, Jun Yu, Yongzhan Nie","doi":"10.1080/17501911.2025.2476380","DOIUrl":"10.1080/17501911.2025.2476380","url":null,"abstract":"<p><p>Gastrointestinal (GI) cancers impose a significant disease burden, underscoring the critical importance of accurate prognosis prediction and treatment response evaluation. DNA methylation, one of the most extensively studied epigenetic modifications, has gained prominence due to its reliable measurement across various sample types. Numerous studies have reported that DNA methylation was linked to the diagnosis, prognosis and treatment response in malignancies, including GI cancers. While its diagnostic role in GI cancers has been comprehensively reviewed. Recent research has increasingly highlighted its potential in prognosis prediction and treatment response evaluation. However, no existing reviews have exclusively focused on these two aspects. In this review, we retrieved relevant studies and included 230 of them in our discussion, thereby providing an overview of the clinical applicability of aberrant DNA methylation in these two fields among patients with esophageal, gastric, colorectal, pancreatic cancers, and hepatocellular carcinomas. Additionally, we discuss the limitations of the current literature and propose directions for future research. Specifically, we emphasize the need for standardized DNA methylation methodologies and advocate for the integration of gene panels, rather than single genes, to address tumor heterogeneity more effectively.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":" ","pages":"475-488"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
EpigenomicsPub Date : 2025-05-01Epub Date: 2025-04-18DOI: 10.1080/17501911.2025.2494497
Chen-Yu Yeh, Wan-Yu Lin
{"title":"Three generations of epigenetic clocks in mediating the adverse effect of smoking on metabolic health.","authors":"Chen-Yu Yeh, Wan-Yu Lin","doi":"10.1080/17501911.2025.2494497","DOIUrl":"https://doi.org/10.1080/17501911.2025.2494497","url":null,"abstract":"<p><strong>Aims: </strong>Metabolic syndrome (MetS) is a composite disorder that includes abdominal obesity, impaired glucose levels, high blood pressure, and dyslipidemia. Smoking can alter epigenetic profiles and is a critical modifiable risk factor for MetS. We aim to explore the epigenetic age acceleration (EAA) that can mainly deliver smoking influences on metabolic health.</p><p><strong>Methods: </strong>We conducted a mediation analysis of 2,474 individuals with data in the Taiwan Biobank. Current and former smoking and the respective pack-years were included as four exposure factors. Seven markers of DNA methylation (DNAm) covering three generations of epigenetic clocks were included as mediators. Seven metabolic outcomes included MetS status (yes vs. no) and six related traits.</p><p><strong>Results: </strong>GrimEAA and DunedinPACE mediated the associations of the four smoking factors with MetS, fasting glucose, triglyceride, and high-density lipoprotein cholesterol levels (false discovery rate < 0.05). GrimEAA and DunedinPACE respectively mediated 48.2% and 24.2% of current smoking's effect on MetS and 60.9% and 26.1% of current smoking pack-year's effect on MetS risk. The DNAm plasminogen activator inhibitor 1 level mediated the adverse effects of current smoking status and pack-years on all seven metabolic outcomes.</p><p><strong>Conclusion: </strong>The GrimEAA-mediated proportions were approximately two times greater than the DunedinPACE-mediated proportions.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":"17 7","pages":"453-461"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"tRF5-22-SerGCT-1 protects the heart against myocardial injury by targeting MSK1.","authors":"Fanji Meng, Hemanyun Bai, Kangling Ke, Lingyan Fang, Haitao Huang, Xiao Liang, Weiyan Li, Xiongwen Chen, Can Chen","doi":"10.1080/17501911.2025.2495544","DOIUrl":"https://doi.org/10.1080/17501911.2025.2495544","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to explore the expression profiles and potential functions of tsRNAs in MI.</p><p><strong>Methods: </strong>Using a mouse model of MI induced by coronary artery ligation, we used smallRNA array to obtain tsRNAs expression profiles. Reverse transcription quantitative polymerase chain reaction(RT-qPCR), Western Blot, tRF5-22-SerGCT-1 mimics and inhibitors, cell proliferation and apoptosis detection, luciferase reporter assay, and bioinformatics analysis were employed to screen differentially expressed tsRNAs and identify the functions of tsRNAs after MI.</p><p><strong>Results: </strong>A total of 175 significantly different tsRNAs (FC > 1.5, <i>p</i> < 0.05) were identified in MI mice, including 98 upregulated and 77 downregulated tsRNAs. Bioinformatics and target gene prediction revealed that two differentially expressed tsRNAs (5'tiRNA-34-GlnCTG-4, tRF5-22-SerGCT-1) may be involved in processes like autophagy and apoptosis, as well as in key signaling pathways such as MAPK and autophagy. Further investigation of tRF5-22-SerGCT-1 revealed that its overexpression or inhibition in vitro affected MSK1 levels and cardiomyocytes apoptosis following oxygen-glucose deprivation, providing a protective effect. Dual-luciferase assays confirmed that tRF5-22-SerGCT-1 targets MSK1.</p><p><strong>Conclusion: </strong>We found differentially expressed tsRNAs in MI. In addition, our research showed first that tRF5-22-SerGCT-1 might be involved in the MAPK pathways by targeting the MSK1, modulating apoptosis.</p>","PeriodicalId":11959,"journal":{"name":"Epigenomics","volume":"17 7","pages":"439-451"},"PeriodicalIF":3.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12026222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}