Environmental Epigenetics最新文献

{"title":"Environmental exposures and epigenetic alterations in common chronic diseases: insights and challenges.","authors":"Cathrine Hoyo, Chantel L Martin, Terrence Allen, David Skaar, Susan K Murphy","doi":"10.1093/eep/dvag014","DOIUrl":"https://doi.org/10.1093/eep/dvag014","url":null,"abstract":"<p><p>Exposure to environmental factors including contaminants and social conditions is implicated in a substantial proportion of common non-communicable diseases, and data from model systems repeatedly demonstrate that the process from environmental contributions to common chronic disease risk is mediated through maladaptive epigenetic responses. The field of environmental epigenetics leverages multiple disciplines to advance our understanding of environmental impacts on epigenomic processes to enhance etiologic investigation, guide biomarker discovery, and identify mechanisms of action that ultimately lead to behavioral and or therapeutic interventions. This article discusses examples of emerging research on the links between three common life course exposures linked to common non-communicable diseases, and their associated epigenetic modifications, with a major focus on DNA methylation-the most studied in humans. It also outlines current challenges when interpreting the accumulating body of knowledge, including the lack of consensus on regions reported to be targeted by these environmental exposures. Finally, given that the strongest predictors of epigenetic states are age and cell/tissue type, strategies to build novel platforms using existing technologies to surmount some of these challenges are discussed. Together, these advances in environmental epigenetics are paving the way for groundbreaking developments toward improved precision in developing prevention and intervention strategies to reduce common non-communicable disease morbidity and mortality.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag014"},"PeriodicalIF":3.2,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13137992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835345","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 mechanisms linking hexavalent chromium exposure to pancreatic cancer risk: a systematic review.","authors":"Kai Hayashi, Yicong Huang, Kenneth R Muir, Artitaya Lophatananon","doi":"10.1093/eep/dvag013","DOIUrl":"https://doi.org/10.1093/eep/dvag013","url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most lethal malignancies, largely due to late diagnosis and limited treatment options. Hexavalent chromium (Cr(VI)) is a well-established environmental and occupational carcinogen, and emerging epidemiological observations have raised questions about its potential involvement in cancers beyond the lung. This systematic review synthesizes current evidence on the epigenetic effects of Cr(VI) exposure, including DNA methylation, histone modifications, and microRNA dysregulation, and evaluates whether these mechanisms converge on pathways relevant to pancreatic carcinogenesis. A structured literature search of EMBASE and PubMed (including MEDLINE) identified 11 studies that met predefined inclusion criteria. Across these studies, Cr(VI) exposure was consistently associated with hypermethylation of tumour suppressor genes (including <i>MLH1</i> and <i>RAD51</i>), alterations in histone methylation (such as increased H3K9me2), and dysregulation of oncogenic microRNAs including miR-3940-5p. Collectively, these epigenetic alterations affect processes central to carcinogenesis, including DNA repair, genomic stability, inflammatory signalling, and cellular stress responses. Notably, several of the genes affected by Cr(VI) exposure such as <i>MLH1, RAD51, CD44</i>, and <i>Nupr1</i> are well-recognized contributors to pancreatic ductal adenocarcinoma (PDAC) development. Although none of the identified studies directly examined Cr(VI)-associated epigenetic changes in pancreatic tissue or pancreatic cell systems, the convergence of Cr(VI)-induced epigenetic alterations on molecular pathways central to PDAC biology highlights a set of biologically plausible and testable hypotheses linking chromium exposure to pancreatic cancer risk. Together, the available evidence suggests that Cr(VI) exposure could plausibly promote pancreatic carcinogenesis through epigenetic silencing of DNA repair pathways and activation of stress-response and stemness-associated signalling networks. By integrating findings across diverse experimental systems, this review identifies mechanistic intersections between chromium-induced epigenetic dysregulation and established drivers of PDAC. These findings highlight a clear opportunity for targeted investigation of Cr(VI)-associated epigenetic signatures in pancreatic-relevant experimental models and in chromium-exposed human populations. Such studies could determine whether environmentally induced epigenetic alterations contribute to pancreatic cancer susceptibility and may reveal previously under-recognized environmental drivers of pancreatic carcinogenesis.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag013"},"PeriodicalIF":3.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766024","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 mechanisms linking the perinatal environment, the placenta, and maternal and child health outcomes: evidence for sexual dimorphism.","authors":"Hadley J Hartwell, Rebecca C Fry","doi":"10.1093/eep/dvag012","DOIUrl":"https://doi.org/10.1093/eep/dvag012","url":null,"abstract":"<p><p>Exposure to adverse environments early in life can shape health trajectories across the lifespan. A key mechanism by which this life-long reprogramming occurs is via epigenetic modifications, including altered DNA methylation (DNAm), histone modifications, and microRNA (miRNA) regulation. This invited perspective highlights key human population studies and selected animal studies from our group and collaborators that have examined toxicant exposure occurring during or prior to pregnancy including metals, pharmaceuticals, microorganisms, air pollution, and socioeconomic stressors and their impact on the epigenome. Exposure to these substances is associated with altered epigenetic patterning in fetal blood and placenta, often in a gene- and sex-specific manner. This gene specificity may be tied to the transcription factor occupancy, where environmental exposures alter transcription factor binding at regulatory regions, influencing downstream epigenetic patterns. In relation to adverse health outcomes, these epigenetic modifications have been associated with adverse pregnancy outcomes such as preeclampsia as well as neonatal health (i.e. preterm birth, retinopathy of prematurity, chronic lung disease, and congenital heart defects). Additionally, these epigenetic alterations have been associated with outcomes later in childhood, including cognition, neurodevelopmental disorders [e.g. autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD)], obesity, metabolic dysregulation, asthma, and immune dysfunction. Collectively, these studies highlight the relationships among early-life environmental factors, epigenetic biomarkers, and maternal and child health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag012"},"PeriodicalIF":3.2,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765975","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":"m⁶A RNA methylation regulatory gene expression in response to ethanol and acetaldehyde exposure and withdrawal.","authors":"Ji Sun Koo, Qiansheng Zhan, Huiping Zhang","doi":"10.1093/eep/dvag011","DOIUrl":"https://doi.org/10.1093/eep/dvag011","url":null,"abstract":"<p><p>⁶-methyladenosine (m⁶A) RNA methylation, regulated by writer, eraser, and reader proteins, modulates mRNA stability, splicing, and translation, thereby influencing key cellular processes. Environmental stressors, such as alcohol, may disrupt this epitranscriptomic machinery and contribute to disease vulnerability. In this study, we investigated how chronic exposure to ethanol, its toxic metabolite acetaldehyde, and subsequent withdrawal affect the expression of m⁶A regulatory genes. Neuron-like (SH-SY5Y) and non-neuronal (SW620) cells were exposed for 3 weeks to ethanol (40 mM) or acetaldehyde (30 μM) (concentrations comparable to blood levels after heavy drinking), followed by a 24-h withdrawal period. Gene expression of seven writers (<i>KIAA1429, METTL3, METTL4, METTL14, RBM15, RBM15B</i>, and <i>WTAP</i>), two erasers (<i>ALKBH5</i>, FTO), and nine readers (<i>YTHDF1/2/3, YTHDC1/2, IGF2BP1/2/3</i>, and <i>HNRNPA2B1</i>) was quantified by RT-qPCR. Concurrently, RNA-seq data from eight reward-related brain regions of 24 individuals of European ancestry (12 with alcohol use disorder [AUD] and 12 controls) were analyzed for AUD-associated expression changes in m⁶A regulatory genes. In cell models, ethanol broadly suppressed the expression of most m⁶A regulatory genes, whereas withdrawal largely restored their levels. Acetaldehyde induced subtler gene expression changes, likely reflecting its lower exposure concentration and rapid metabolism. Postmortem brain analysis revealed trends toward altered expression of m⁶A regulatory genes across multiple brain regions in individuals with AUD. Collectively, these findings suggest that chronic alcohol exposure dysregulates m⁶A regulatory gene expression and may impact downstream RNA regulatory pathways involved in AUD pathophysiology. Further studies are warranted to elucidate the mechanisms by which alcohol-induced dysregulation of m⁶A regulators influences AUD risk.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag011"},"PeriodicalIF":3.2,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671495","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":"Transgenerational reproductive risks of BPA: epigenetic mechanisms and biomarker applications. A critical review.","authors":"Okon Michael Ben, Olorunnisola Sinbad Olubukola, Ifie Josiah Eseoghene, Ugwu Okechukwu Paul-Chima, Alum Esther Ugo, Mounmbegna Philippe, Aja Patrick Maduabuchi","doi":"10.1093/eep/dvag010","DOIUrl":"https://doi.org/10.1093/eep/dvag010","url":null,"abstract":"<p><p>Bisphenol A (BPA), which is a common ingredient of plastics and epoxy resins, is among the most commonly found endocrine-disrupting chemicals in the human environment. Chronic human exposure has raised concerns over its effects on reproductive health. There is growing evidence showing that BPA causes epigenetic changes, primarily DNA methylation, histone changes, and non-coding RNA changes that result in hormonal imbalances, a disruption in gametogenesis, and fertility impairment. This review summarizes current understanding of how BPA alters male reproductive performance in exposed individuals, including impaired spermatogenesis and sperm quality, endocrine imbalance, and disruption of hypothalamic-pituitary-gonadal (HPG) signaling, often in concert with oxidative stress and altered steroidogenesis. We then discuss evidence that BPA exposure, especially during critical developmental windows, can reprogram the paternal germline, such that epigenetic alterations carried by sperm, such as DNA methylation changes, abnormal histone acetylation (H3K9ac, H3K27ac, H4K12ac), disrupted histone-to-protamine transition, and altered sperm small RNAs/miRNA profiles, can contribute to fertility defects in subsequent generations. Moreover, various therapeutic methods, like epigenetic drugs and natural products such as resveratrol, naringenin, and genistein, are being studied to reverse or alleviate the impact of BPA. Given BPA's ubiquity, these findings also highlight the necessity of stricter regulation, health education to the general population, along with research into potential safer alternatives. Learning the ways BPA is remodeling the epigenome and fertility through generations is essential to protecting reproductive health and the basis of policy intervention.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag010"},"PeriodicalIF":3.2,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671556","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":"A systematic review investigating the relationship between green and blue spaces and depression in older adults via DNA methylation.","authors":"Jacob Illyuk, Sophie Glover, Shea A Walsh, Anna Jurek-Loughrey, Amy Jayne McKnight, Ruth F Hunter","doi":"10.1093/eep/dvag009","DOIUrl":"https://doi.org/10.1093/eep/dvag009","url":null,"abstract":"<p><p>Depression in older adults has been associated with negative health outcomes, such as dementia. Previous research has demonstrated that green and blue spaces, defined as areas of vegetation or bodies of water respectively, are beneficial to mental health, although the biological mechanisms are poorly understood. One of the mechanisms proposed is DNA methylation (DNAm). DNAm is an epigenetic process that alters gene expression. Changes in methylation have been observed in those with depression, and associated with green space exposure, while blue spaces have been shown to reduce the risk of depression. Using a mechanistic review approach, we investigated the relationships of green space and depression with DNAm with the aim of identifying potential overlapping mechanisms. In the environmental search, keywords such as 'green space' and 'DNAm' were combined. In the mental health search, keywords such as 'DNAm' and 'depression' were combined. From a total of 45 695 papers returned, four studies on green space, and five studies on depression met the eligibility criteria for this review. All included studies reported significant or suggestively significant methylation sites. No overlapping CpG sites were identified when comparing methylation changes found in response to green space and depression. Changes in the <i>RGS12</i> gene were associated with both depression and green space exposure. DNAm is a biological mechanism that may contribute to the impact of exposure to green space; further research is warranted to better understand DNAm as a mechanistic pathway between green space and depression.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag009"},"PeriodicalIF":3.2,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835273","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":"Seasonal timing in a changing world: the epigenetic link between environment and reproduction across taxa.","authors":"Heidi M Viitaniemi, Tyler J Stevensson, Arild Husby","doi":"10.1093/eep/dvag008","DOIUrl":"10.1093/eep/dvag008","url":null,"abstract":"<p><p>All plants and animals must time their annual reproduction to seasonal variation in resources to optimize reproductive fitness. Environmental factors such as photoperiod and temperature are well known to influence seasonal timing of reproduction but how organisms incorporate environmental cues to alter physiological responses and initiate reproduction remains poorly characterized at the genetic level. A growing number of studies have found that epigenetic mechanisms, such as noncoding RNA, histone modification, and DNA methylation, can have an important role in modifying transcriptional regulation of traits related to seasonal timing. While epigenetic modifications act differently across taxa, there is consistent evidence for their involvement in the timing of seasonal life-history transitions. Here, we discuss the way in which environmental cues trigger epigenetic modifications and propose several roles for their involvement in the regulation of seasonal phenotypes in plants, invertebrates, and vertebrates.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag008"},"PeriodicalIF":3.2,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007883/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510747","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 as a biomarker of prenatal exposures: current challenges and opportunities.","authors":"Rachel B Walkup, Matthew A Nangle, Phillip E Bergmann, Robert J Lipinski","doi":"10.1093/eep/dvag006","DOIUrl":"https://doi.org/10.1093/eep/dvag006","url":null,"abstract":"<p><p>The prenatal environment contributes to the risk for congenital conditions, including birth defects, developmental disorders, and diseases that manifest in later life. However, our current understanding of prenatal exposures and their impact on disease risk is extremely limited. DNA methylation (DNAm) is a promising biomarker of prenatal exposures because this epigenetic mechanism is developmentally active, environmentally responsive, and imparts chemically stable marks that can be quantified with increasing accuracy and precision. However, development and utilization of DNAm biomarkers are impeded by inadequate understanding of how environmentally responsive prenatal DNAm changes persist across progenitor cell populations and pre- and postnatal development. This review synthesizes current evidence on the impact of the prenatal environment on DNAm, including specific dietary and chemical influences, and persistence of these changes across life stages. We then evaluate the suitability of common surrogate tissues (blood, saliva, and extra-embryonic tissues) from a developmental cell lineage framework for their applicability in prenatal exposure research and outline key considerations in selecting surrogate tissues for epigenome-wide association studies. Finally, using orofacial cleft etiopathogenesis as a model, we illustrate the conceptual application of DNAm biomarkers and highlight the need for longitudinal studies and comparative analysis of target and surrogate tissues. By identifying key knowledge gaps and proposing actionable strategies to address them, this review is directed at advancing the use of DNAm biomarkers in resolving how prenatal exposures contribute to human disease.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag006"},"PeriodicalIF":3.2,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282994","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":"Diazinon may increase the risk of acute lymphoblastic leukemia by inducing <i>MGMT</i> promoter methylation.","authors":"Arash Rafeeinia, Mehrnaz Karimi Darabi, Reza Sadeghi, Hadi Bazyar, Fatemeh Saeed, Mostafa Dianati","doi":"10.1093/eep/dvag005","DOIUrl":"https://doi.org/10.1093/eep/dvag005","url":null,"abstract":"<p><strong>Background and objective: </strong>Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy, which is impacted by genetic, epigenetic, and environmental variables. Aberrant methylation of genes, such as O6-methylguanine-DNA-methyltransferase (<i>MGMT</i>), is one of the key mechanisms in carcinogenesis. The aim of the present study was to examine the association of exposure to diazinon with <i>MGMT</i> gene methylation and expression levels in children with ALL.</p><p><strong>Methods: </strong>This case-control research was performed on 136 children with ALL and 136 healthy children as the control group. Demographic data were gathered using a questionnaire and blood sampling. Serum concentrations of diazinon were determined using gas chromatography (GC). DNA was extracted from nucleated cells, followed by bisulfite treatment and examination of <i>MGMT</i> gene promoter methylation using methylation-specific polymerase chain reaction (MSP). Gene expression levels were also determined using real-time Polymerase chain reaction (PCR). Acetylcholinesterase (AChE) activity and malondialdehyde (MDA) concentrations were evaluated as indicators of pesticide toxicity and oxidative stress.</p><p><strong>Results: </strong>Diazinon levels were significantly increased in ALL patients compared to controls (<i>P</i> < .001) and were positively associated with elevated methylation levels of <i>MGMT</i> gene promoter. The odds ratio of ALL development was significantly higher in children with both increased diazinon concentrations and elevated <i>MGMT</i> methylation levels. Moreover, patients exhibited reduced AChE activity and higher MDA concentrations, suggesting the induction of neurotoxicity and oxidative stress triggered by diazinon.</p><p><strong>Conclusion: </strong>Exposure to diazinon might contribute to the development and progression of ALL by triggering aberrant methylation of the <i>MGMT</i> gene, decreasing DNA repair capacity, and promoting oxidative damage. This study highlights the importance of minimizing pesticide exposure and suggests the use of <i>MGMT</i> methylation as a biomarker for the diagnosis and prognosis of ALL.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag005"},"PeriodicalIF":3.2,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12926663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282942","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":"Genome-wide DNA methylation changes after 24 hours at high altitude.","authors":"Shyleen Frost, Kathy Pham, Erica C Heinrich","doi":"10.1093/eep/dvag004","DOIUrl":"https://doi.org/10.1093/eep/dvag004","url":null,"abstract":"<p><p>High altitude presents a significant environmental stressor in the form of hypobaric hypoxia. The body responds to this condition with various acclimatization mechanisms, yet the role of epigenetic modifications, particularly DNA methylation, remains unclear. To address this gap, we investigated DNA methylation patterns in response to acute high-altitude exposure. Twelve healthy sea-level residents, aged 19-32 years, traveled to 3800 m, and DNA from peripheral blood mononuclear cells was collected both at sea level and after 24 h at high altitude. DNA methylation was assessed using the Illumina MethylationEPIC array. We identified 58,046 differentially methylated positions at high altitude compared to sea level, with a large majority of these sites showing increased methylation levels at high altitude, supporting the hypothesis that acute exposure to hypoxia may result in global hypermethylation. Notably, differentially methylated sites were located in genes enriched for pathways related to the hypoxia-inducible factor (HIF) pathway, such as \"Notch signaling\" and \"AKT1 signaling in cancer.\" Moreover, several pathways associated with calcium regulation and DNA damage repair were implicated, suggesting an association between DNA methylation and calcium processes affected by hypoxia. In addition to single positions, we explored differentially methylated regions, resulting in top differentially methylated regions being associated with calcium processes, zinc finger proteins, glucose processes, and erythropoiesis. These findings provide insight into how short-term environmental hypoxia may influence the human epigenome, highlighting DNA methylation as a dynamic marker of environmental exposure.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag004"},"PeriodicalIF":3.2,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347361","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}