Epigenomes最新文献

{"title":"Epigenomic Interactions Between Chronic Pain and Recurrent Pressure Injuries After Spinal Cord Injury.","authors":"Letitia Y Graves, Melissa R Alcorn, E Ricky Chan, Katelyn Schwartz, M Kristi Henzel, Marinella Galea, Anna M Toth, Christine M Olney, Kath M Bogie","doi":"10.3390/epigenomes9030026","DOIUrl":"10.3390/epigenomes9030026","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI).</p><p><strong>Methods: </strong>Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA.</p><p><strong>Results: </strong>Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for <i>BLCAP/NNAT</i> are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene <i>FDFT1</i> were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups.</p><p><strong>Conclusions: </strong>DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979672","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}

{"title":"Exploring Epigenetic Ageing Using Direct Methylome Sequencing.","authors":"Elena-Cristina Găitănaru, Roua Gabriela Popescu, Andreea-Angelica Stroe, Sergiu Emil Georgescu, George Cătălin Marinescu","doi":"10.3390/epigenomes9030025","DOIUrl":"10.3390/epigenomes9030025","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Advances in nanopore sequencing have opened new avenues for studying DNA methylation at single-base resolution, yet their application in epigenetic ageing research remains underdeveloped. <b>Methods</b>: We present a novel framework that leverages the unique capabilities of nanopore sequencing to profile and interpret age-associated methylation patterns in native DNA. <b>Results</b>: Unlike conventional array-based approaches, long reads sequencing captures full CpG context, accommodates diverse and repetitive genomic regions, removes bisulfite conversion steps, and is compatible to the latest reference genome. <b>Conclusions</b>: This work establishes nanopore sequencing as a powerful tool for next-generation epigenetic ageing studies, offering a scalable and biologically rich platform for anti-ageing interventions monitoring and longitudinal ageing studies.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700439","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}

{"title":"Trends in DNA Methylation over Time Between Parous and Nulliparous Young Women.","authors":"Su Chen, John W Holloway, Wilfried Karmaus, Hongmei Zhang, S Hasan Arshad, Susan Ewart","doi":"10.3390/epigenomes9030024","DOIUrl":"10.3390/epigenomes9030024","url":null,"abstract":"<p><strong>Background/objectives: </strong>The experience of pregnancy and parturition has been associated with long-term health effects in mothers, imparting protective effects against some diseases while the risk of other diseases is increased. The mechanisms that drive these altered disease risks are unknown. This study examined DNA methylation (DNAm) changes from pre-pregnancy to several years after giving birth in parous women compared to nulliparous controls over the same time interval.</p><p><strong>Methods: </strong>Using 180 parous-associated CpGs, three analyses were carried out to test DNAm changes from pre-pregnancy at age 18 years to gestation; from gestation to post-pregnancy at age 26 years in parous women; and from 18 to 26 years in nulliparous women using linear mixed models with repeated measures.</p><p><strong>Results: </strong>The directions of DNAm changes were the same between the parous and nulliparous groups. Most CpG dinucleotides (67%, 121 of 180) had a decreasing trend while a small number (7%, 13 of 180) had an increasing trend. Of the CpGs showing increasing or decreasing DNAm, approximately half had DNAm change to a smaller extent in parous women and the other half changed more in parous women than nulliparous controls. 9% (17 of 180) changed significantly in nulliparous women only, leading to a significant difference in DNAm levels in parous women at the post-pregnancy 26 years time point.</p><p><strong>Conclusions: </strong>Pregnancy and parturition may accelerate methylation changes in some CpGs, but slow down or halt methylation changes over time in other CpGs.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700441","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}

{"title":"The Fundamental Role of Nutrients for Metabolic Balance and Epigenome Integrity Maintenance.","authors":"Ana Paula de Souza, Vitor Marinho, Marcelo Rocha Marques","doi":"10.3390/epigenomes9030023","DOIUrl":"10.3390/epigenomes9030023","url":null,"abstract":"<p><p>Epigenetic modifications act as crucial regulators of gene activity and are influenced by both internal and external environmental factors, with diet being the most impactful external factor. On the other hand, cellular metabolism encompasses a complex network of biochemical reactions essential for maintaining cellular function, and it impacts every cellular process. Many metabolic cofactors are critical for the activity of chromatin-modifying enzymes, influencing methylation and the global acetylation status of the epigenome. For instance, dietary nutrients, particularly those involved in one-carbon metabolism (e.g., folate, vitamins B12 and B6, riboflavin, methionine, choline, and betaine), take part in the generation of S-adenosylmethionine (SAM), which represents the main methyl donor for DNA and histone methylation; α-ketoglutarate and ascorbic acid (vitamin C) act, respectively, as a co-substrate and cofactor for Ten-eleven Translocation (TET), which is responsible for DNA demethylation; and metabolites such as Acetyl-CoA directly impact histone acetylation, linking metabolism of the TCA cycle to epigenetic regulation. Further, bioactive compounds, such as polyphenols, modulate epigenetic patterns by affecting methylation processes or targeting epigenetic enzymes. Since diet and nutrition play a critical role in shaping epigenome functions and supporting human health, this review offers a comprehensive update on recent advancements in metabolism, epigenetics, and nutrition, providing insights into how nutrients contribute to metabolic balance, epigenome integrity maintenance and, consequently, disease prevention.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 3","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12286010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700440","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}

{"title":"Methylation of the Glucocorticoid Receptor Gene in Children with Somatic Symptom Disorder: A Case-Control Study.","authors":"Kyoko Hatta, Masato Kantake, Kyoko Tanaka, Hirofumi Nakaoka, Toshiaki Shimizu, Hiromichi Shoji","doi":"10.3390/epigenomes9020022","DOIUrl":"10.3390/epigenomes9020022","url":null,"abstract":"<p><p><b>Background:</b> Somatic symptom disorder (SSD) in children may be influenced by stress reactivity and psychosocial factors. The glucocorticoid receptor (GR), encoded by NR3C1, is a key mediator of stress responses. However, the relationship between NR3C1 methylation and SSD remains unclear. <b>Methods:</b> We analyzed NR3C1 exon 1F methylation in cell-free DNA from saliva in 34 children with SSD and 29 age- and sex-matched controls using bisulfite amplicon sequencing. Psychological assessments included the Beck Depression Inventory-II (BDI-II) and KINDL questionnaires to evaluate associations with methylation patterns. <b>Results:</b> Methylation levels showed age-related differences. In children under 13, CpG sites displayed mixed methylation, and specific sites correlated with KINDL and BDI-II scores. KINDL physical and total well-being scores negatively correlated with CpG30 and positively with CpG35; BDI-II scores negatively correlated with CpG32 and CpG35. In children aged 13 or older, CpG sites showed uniformly high methylation with no correlation to psychological measures. The SSD group showed significantly higher average methylation across the exon 1F region than controls in the older age group. These children also had more cases of orthostatic dysregulation and longer illness duration. <b>Conclusions:</b> This study suggests age-dependent epigenetic regulation of NR3C1 in SSD. While younger children showed CpG-specific correlations with psychological symptoms, older children demonstrated uniformly high methylation and potentially reduced gene expression, potentially reflecting cumulative stress, autonomic dysfunction, and internalizing disorders such as anxiety and depression.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487234","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}

{"title":"The Dynamic Interactions of m6A Modification and R-Loops: Implications for Genome Stability.","authors":"Nicholas Kim, Hong Sun","doi":"10.3390/epigenomes9020021","DOIUrl":"10.3390/epigenomes9020021","url":null,"abstract":"<p><p>R-loops, three-stranded RNA-DNA hybrid nucleic acid structures, are recognized for their roles in both physiological and pathological processes. Regulation of R-loops is critical for genome stability as disruption of R-loop homeostasis can lead to aberrant gene expression, replication stress, and DNA damage. Recent studies suggest that the RNA modification, N6-methyladenosine (m6A), can modify R-loops and the writers, erasers, and readers of m6A are involved in the dynamic regulation of R-loops. Here, we discuss the reported functions of various m6A regulatory proteins in relation to R-loops, highlighting their distinct roles in recognizing and modulating the formation, stability, and resolution of these structures. We further examine the functional implications of m6A and R-loop interaction in human diseases, with a particular emphasis on their roles in cancer.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487235","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}

{"title":"Epigenetic Insights into Tuberous Sclerosis Complex, Von Hippel-Lindau Syndrome, and Ataxia-Telangiectasia.","authors":"Gavriel Hadjigavriel, Christina Stylianides, Evangelos Axarloglou, Maria Eleni Manthou, Efstratios Vakirlis, Paschalis Theotokis, Soultana Meditskou, Iasonas Dermitzakis","doi":"10.3390/epigenomes9020020","DOIUrl":"10.3390/epigenomes9020020","url":null,"abstract":"<p><p>Neurocutaneous syndromes represent a clinically and genetically heterogeneous group of disorders, with tuberous sclerosis complex (TSC), von Hippel-Lindau syndrome (VHL), and ataxia-telangiectasia (A-T) exemplifying some of the most complex entities within this category. These syndromes have traditionally been considered monogenic disorders, caused by germline mutations in tumor suppressor or regulatory genes. However, they exhibit a striking degree of phenotypic variability and divergent clinical trajectories that cannot be fully explained by their underlying genetic alterations alone. Increasingly, epigenetic regulatory mechanisms, such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNA (ncRNA) activity, are recognized as key modulators of gene expression, cellular differentiation, and tissue-specific function. Disruption of these mechanisms has been implicated in disease pathogenesis, tumorigenesis, and neurodegeneration associated with TSC, VHL, and A-T. Aberrant epigenetic profiles may underlie the observed variability in clinical outcomes, even among individuals with identical mutations. This review consolidates current evidence on the epigenetic landscape of these syndromes, elucidating how these modifications may influence disease behavior and contribute to incomplete genotype-phenotype correlations. By integrating epigenetic insights with known molecular pathways, a more nuanced understanding of disease biology emerges, with potential implications for diagnostic stratification, prognostic assessment, and therapeutic innovation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487231","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}

{"title":"Association of Model-Predicted Epigenetic Age and Female Infertility.","authors":"Elena Pozdysheva, Vitaly Korchagin, Tatiana Rumyantseva, Daria Ogneva, Vera Zhivotova, Irina Gaponova, Konstantin Mironov, Vasily Akimkin","doi":"10.3390/epigenomes9020019","DOIUrl":"10.3390/epigenomes9020019","url":null,"abstract":"<p><strong>Background: </strong>To date, there are no precise clinical and laboratory methods to accurately predict the onset of fertility decline in women, with chronological age being the ultimate predictor. This has led to increased interest in developing methods to determine biological age, as it provides a more accurate understanding of individual age-related physiological changes.</p><p><strong>Methods: </strong>In this study, we developed a model for estimating biological age based on DNA methylation levels in the <i>ELOVL2</i>, <i>TRIM59</i>, <i>C1orf132</i>, <i>FHL2</i>, and <i>KLF14</i> genes using pyrosequencing. The model was tested in 64 Russian women, aged 25-39 years, to find an association between epigenetic age, infertility, low anti-Müllerian hormone (AMH) levels, and assisted reproductive technology (ART) failure.</p><p><strong>Results: </strong>The predictive performance of the model was evaluated. The mean absolute deviation of the model was 2.8 years; the mean absolute error was 2.6 years (R² = 0.95). In the studied cohort, 33% of women exhibited epigenetic age acceleration (EAA), while 45% showed epigenetic age deceleration (EAD). All women with an EAA of ≥3 years (n = 6) had a history of infertility.</p><p><strong>Conclusions: </strong>In this study, no statistically significant associations were observed between EAA/EAD and AMH, body mass index, infertility, or ART failure in women.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487228","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}

{"title":"DNA Methylation, Aging, and Cancer.","authors":"Himani Vaidya, Jaroslav Jelinek, Jean-Pierre J Issa","doi":"10.3390/epigenomes9020018","DOIUrl":"10.3390/epigenomes9020018","url":null,"abstract":"<p><p>Aging and cancer, though distinct biological processes, share overlapping molecular pathways, particularly in epigenetic regulation. Among these, DNA methylation is central to mediating gene expression, maintaining cellular identity, and regulating genome stability. This review explores how age-associated changes in DNA methylation, characterized by both global hypomethylation and focal hypermethylation, contribute to the emergence of cancer. We discuss mechanisms of DNA methylation drift, the development of epigenetic clocks, and the role of entropy and epigenetic mosaicism, in aging and tumorigenesis. Emphasis is placed on how stochastic methylation errors accumulate in aging cells and lead to epiallelic shifts and gene silencing, predisposing tissues to malignant transformation, even despite recently increased cancer incidences at younger ages. We also highlight the translational potential of DNA methylation-based biomarkers, and therapeutic targets, in age-related diseases. By framing cancer as a disease of accelerated epigenetic aging, this review offers a unifying perspective and calls for age-aware approaches to both basic research and clinical oncology.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487229","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}

{"title":"Epigenetic DNA Methylation Under the Influence of Low-Dose Ionizing Radiation, and Supplementation with Vitamin B12 and Folic Acid: Harmful or Beneficial for Professionals?","authors":"Borivoje Savic, Bozidar Savic, Svetlana Stanojlovic","doi":"10.3390/epigenomes9020017","DOIUrl":"10.3390/epigenomes9020017","url":null,"abstract":"<p><p>This review paper highlights the importance of educating current and future professionals about epigenetic mechanisms and recognizing epigenetics as a crucial model for protection against ionizing radiation. Two basic models for radiation-induced DNA damage are currently in use. The association between mutations and chromosomal aberrations provides a framework for analyzing risks at low radiation doses and exposure to small doses. However, there is no monitoring of epigenetic changes in professionals exposed to low doses of ionizing radiation. Epigenetic events regulate gene activity and expression not only during cell development and differentiation but also in response to environmental stimuli, such as ionizing radiation. Furthermore, the potential occurrence of malignant and hereditary diseases at low doses of ionizing radiation is linearly correlated and is considered a scientifically accepted assumption, despite recognized scientific limitations associated with this assessment. The aim of this review is to integrate novel and intriguing radiobiological paradigms regarding the effects of ionizing radiation on DNA methylation and epigenetic regulation of the DNA molecule. Several hypothesized biological responses to ionizing radiation are examined, linking them to epigenetic mechanisms involved in health risk assessment for professionals. The second part of the review includes published research related to epigenetics, supplementation, and virus reactivation in the context of epigenetic modifications of the DNA molecule. We hypothesize that different cycles lead to changes in the epigenome, which may be associated with the reactivation of certain viruses and the deficiency of specific dietary elements. These findings are linked to minimal deficiencies in vitamin B12 and folic acid, which may contribute to epigenomic changes. This aspect is crucial for the immune status of individuals working in high-risk environments.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"9 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487230","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}