Albert Menéndez-Pedriza, Janan Gawra, Jorke H Kamstra, Melissa Faria, Marina Bellot, Cristian Gómez-Canela, Demetrio Raldúa, Juliette Legler, Joaquim Jaumot, Benjamin Piña, Laia Navarro-Martín
{"title":"Integrative multi-omic analysis reveals epigenetic and neurotransmitter signaling disruption induced by tributyltin in zebrafish eleutheroembryos.","authors":"Albert Menéndez-Pedriza, Janan Gawra, Jorke H Kamstra, Melissa Faria, Marina Bellot, Cristian Gómez-Canela, Demetrio Raldúa, Juliette Legler, Joaquim Jaumot, Benjamin Piña, Laia Navarro-Martín","doi":"10.1093/eep/dvag031","DOIUrl":"10.1093/eep/dvag031","url":null,"abstract":"<p><p>Environmental exposure to endocrine disruptors such as Tributyltin (TBT) has been established as a serious threat causing neurological impairment, reproduction dysfunction and lipid dysregulation. However, the molecular mechanisms underlying TBT-induced toxicity, particularly its capacity to disrupt epigenetic programming during critical developmental windows, remain poorly understood. State-of-the-art multi-omic approaches have emerged to consider the complexity of the different omic systems, crucial for a better characterization of the mechanisms of action of pollutants. In the present study, a novel multi-omic analysis integrating epigenomics, transcriptomics, and metabolomics was conducted on zebrafish eleutheroembryos exposed from 2 to 5 days post-fertilization to two non-toxic TBT concentrations (3 and 30 nM). To capture not only the toxic mechanisms but also multifaceted molecular interactions from gene to phenotype, multi-omics results were complemented by behavioural and neurotransmitter content analyses at the end of the exposures and after a 3-day clearance period. TBT induced the appearance of 5 280 differentially methylated regions, with significant enrichment in intergenic, CpG islands, and promoter regions. Our results also revealed that altered differentially methylated regions were involved in key biological processes, including nervous system development, synaptic signaling, and muscle structure development. Multi-omic analysis identified significant alterations in neurotransmitter signaling pathways, which were then confirmed through neurotransmitter content analysis. TBT also affected responses at the organismal level, particularly impairing cognitive performance. Altogether, the integration of multi-omic strategies demonstrated the potential to revolutionize the future of toxicology by enhancing the understanding of environmental pollutant effects, paving the way for more refined risk assessment and regulatory frameworks.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag031"},"PeriodicalIF":4.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215308","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}
Ustat Bedi, Ingrid Melle, Ole A Andreassen, Anne Kristin Stavrum, Stephanie Le Hellard
{"title":"Seasonal influences on DNA methylation at birth or at sampling time and their interaction with psychosis risk.","authors":"Ustat Bedi, Ingrid Melle, Ole A Andreassen, Anne Kristin Stavrum, Stephanie Le Hellard","doi":"10.1093/eep/dvag033","DOIUrl":"https://doi.org/10.1093/eep/dvag033","url":null,"abstract":"<p><strong>Background: </strong>Season at birth has been associated with increased risk for psychotic disorders. Epigenetic markers, which can be influenced by environmental exposures, may help to understand the mechanisms of seasonal effects.</p><p><strong>Aims: </strong>To investigate two types of seasonal influences on DNA methylation: season of sampling and season of birth, and to test whether these seasonal effects interact with psychotic disorder risk.</p><p><strong>Methods: </strong>We used two cohorts: a sample of newborns from the Norwegian Mother, Father, and Child Study (MoBa) and a sample of adult participants from the Thematically Organized Psychosis (TOP) sample. The cosinor function from the R package \"seasons\" was used to identify seasonally methylated positions (SMPs) associated with season of birth and season of sampling. Meta-analyses were performed between results from the MoBa birth cohort, and the TOP healthy adults samples for both season of birth and season of sampling. Interaction analyses between season of birth/season of sampling and psychosis status were conducted in the TOP cohort.</p><p><strong>Results: </strong>In the meta-analysis of healthy controls from our cohorts, we identified six SMPs (<i>IQSEC1, CACNA2D3, TMEM86B, CNOT3, ZNF250</i>, and <i>ARHGEF3)</i> and two SMPs (<i>ZNF250</i> and <i>SLC6A19)</i> associated with season of sampling and season of birth, respectively. In the interaction analysis, one significant SMP (cg13593913,) was found to be associated with a psychosis diagnosis and season of birth.</p><p><strong>Conclusion: </strong>In our study, we show a potential interaction between season of birth and psychosis diagnosis. These findings highlight the importance of considering the season of birth and season of sampling in epigenetic research.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag033"},"PeriodicalIF":4.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180283","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}
Holly V Moeller, Hollie M Putnam, Ross Cunning, Steven B Roberts, Jose M Eirin-Lopez, Roger M Nisbet
{"title":"Epigenetic intelligence: how organisms track their environment through molecular memory.","authors":"Holly V Moeller, Hollie M Putnam, Ross Cunning, Steven B Roberts, Jose M Eirin-Lopez, Roger M Nisbet","doi":"10.1093/eep/dvag032","DOIUrl":"10.1093/eep/dvag032","url":null,"abstract":"<p><p>The regulation of gene expression by epigenetic markers is a growing area of focus for researchers who seek to explain rapid phenotypic acclimatization to environmental change. Yet even as empirical datasets accumulate exponentially, the mechanistic underpinnings of epigenetic changes and their role in connecting environmental variation with the regulation of gene function remain unclear. Here, we use a stochastic model of epigenetic change to generate three testable predictions: (1) that organisms require environmental feedback to track their environments through epigenetic responses, (2) that this tracking requires coordination between the addition and removal of epigenetic markers, and (3) that epigenetically driven tracking is only effective under specific subsets of environmental variability. Despite the intuitiveness of these postulates, few to no experimental studies directly test them. Using marine invertebrates as a case study, we review correlational evidence consistent with the model's predictions, describe hypothetical mechanisms by which epigenetic strategies could evolve, and clearly identify knowledge gaps and urgent experimental needs in the field. Overall, the field of environmental epigenetics is poised for major advances, which can be enhanced through the continued synthesis of mathematical frameworks and empirical data.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag032"},"PeriodicalIF":4.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215278","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}
Maria A Dimitriu, Ellen Jaspers, Eduardo Cáceres Pajuelo, Lea Rettich, Theresa Schöpp, Leonard C Steg, Leonardo Zingler-Herrero, Anna Chamot, Rodrigo G Arzate-Mejia, Isabelle M Mansuy
{"title":"Symposium report- epigenetic inheritance: impact for biology and society 27-29 August 2025, Zurich, Switzerland.","authors":"Maria A Dimitriu, Ellen Jaspers, Eduardo Cáceres Pajuelo, Lea Rettich, Theresa Schöpp, Leonard C Steg, Leonardo Zingler-Herrero, Anna Chamot, Rodrigo G Arzate-Mejia, Isabelle M Mansuy","doi":"10.1093/eep/dvag028","DOIUrl":"10.1093/eep/dvag028","url":null,"abstract":"<p><p>Epigenetic inheritance is a form of transmission of features or traits acquired by experience or environmental exposure that does not involve any changes in the DNA sequence unlike genetic heredity. Epigenetic inheritance is actively studied in animal models and humans and has major implications for biology, health, and society. While it is well established in plants and invertebrates, its mechanisms and importance in mammals have not been fully delineated. Several key questions remain open for instance, which life experiences and environmental exposures can induce heritable phenotypic changes and how induced changes can be propagated from exposed parents to descendants, and whether and how germ cells contribute to such inheritance. These questions were the focus of the fifth edition of the symposium \"Epigenetic Inheritance: Impact for Biology and Society\" held in Zurich, Switzerland, on 27-29 August 2025. They were discussed by experts from diverse disciplines who presented epidemiological data in humans, results in animal models, new findings on transmission mechanisms, methodological advances, and societal and evolutionary implications. This report summarizes the research presented during the symposium and highlights current conceptual and technical challenges. It also presents other scientific activities during the symposium, which included poster sessions, an art exhibition, and a documentary movie on war trauma across generations.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag028"},"PeriodicalIF":4.3,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873475","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}
Kumaraswamy Naidu Chitrala, Danielle L Beatty Moody, Nicolle A Mode, Botong Shen, Nicole Noren Hooten, Alan B Zonderman, Ngozi Ezike, Michele K Evans
{"title":"Investigation of psychosocial stress and DNA methylation in genes related to immune response, metabolism, and calcium signaling among African American and White middle-aged adults.","authors":"Kumaraswamy Naidu Chitrala, Danielle L Beatty Moody, Nicolle A Mode, Botong Shen, Nicole Noren Hooten, Alan B Zonderman, Ngozi Ezike, Michele K Evans","doi":"10.1093/eep/dvag030","DOIUrl":"10.1093/eep/dvag030","url":null,"abstract":"<p><p>Chronic psychological stress is an environmental factor associated with chronic disease risk and health disparities. Since environmental stressors alter gene expression and physiologic responses through epigenetic mechanisms, perceived discrimination (PD), or the subjective experience of receiving negative treatment related to personal characteristics may influence DNA methylation (DNAm) of CpGs within genes linked to chronic disease. Using the Illumina 850K EPIC chip and psychosocial stress-associated discrimination scales, including the lifetime, racial, and everyday discrimination scales, we identified novel CpGs and differentially methylated positions (DMPs) associated with PD in the context of age, sex, and poverty status among African American and White adults and ones that overlap previous findings of differentially methylated sites (or genes) with discrimination, inflammation, and chronic disease. Ingenuity Pathway Analysis identified several pathways associated with the DNAm patterns and PD with age, sex, and/or poverty status. With age, the white adipose tissue browning pathway was activated among African American participants. This was related to the differential methylation found in the <i>CACNA1H, PRDM16</i>, and <i>BDNF</i> genes. Among White participants, the opioid signaling pathway was activated and significantly enriched for the genes <i>FGR, POMC</i>, and <i>RPS6KA2</i>. Additionally, CpG sites associated with PD among White participants with poverty status revealed that the netrin signaling, opioid signaling, and calcium signaling pathways were activated and significantly enriched for differentially methylated genes, including <i>NFATC1 and NFATC2</i>. The identified novel DNAm genes associated with PD transduce effects through biological pathways related to inflammation and immune response, white adipose tissue browning, and calcium signaling.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag030"},"PeriodicalIF":4.3,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896689","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}
Margarett Shnorhavorian, John K Amory, Stephen M Schwartz, Smita Bhatia, Saro Armenian, Holcombe E Grier, Eric J Chow, Rashmi Joshi, Daniel Beck, Michael K Skinner
{"title":"Weighted epigenetic site correlation network analysis of chemotherapy impacts on osteosarcoma cancer survivors' male fertility, sperm, and endocrine parameters.","authors":"Margarett Shnorhavorian, John K Amory, Stephen M Schwartz, Smita Bhatia, Saro Armenian, Holcombe E Grier, Eric J Chow, Rashmi Joshi, Daniel Beck, Michael K Skinner","doi":"10.1093/eep/dvag029","DOIUrl":"10.1093/eep/dvag029","url":null,"abstract":"<p><p>The impacts of chemotherapy exposure on adolescent male osteosarcoma survivors as adults were investigated using a number of physiological parameters, with a focus on chemotherapy, reproduction, and sperm. The Children's Oncology Group (COG) clinical sites (protocol ALTE16C1) of previously collected and stored sperm samples were obtained for this analysis. The epigenetic DNA methylation alterations in sperm were assessed in 176 control adult male patients' sperm, and 183 chemotherapy-exposed osteosarcoma survivors' adult male sperm were provided by COG sites. The current study used a weighted gene co-expression network analysis computational approach that was adopted for use as a weighted epigenetic site correlation network analysis. This analysis identified correlation coefficients between differential DNA methylation regions and other DNA methylation sites with physiological and chemotherapy parameters. Module-trait relationships in the data were determined for epigenetic modules, which highly correlated with sperm parameters, reproductive hormones, and several chemotherapies (e.g. cisplatin). Gene associations of these epigenetic sites were identified and correlated to chemotherapy-associated genes and pathways, as well as reproductive parameters. Observations demonstrate dramatic impacts of adolescent chemotherapy on later adult life sperm epigenetics. Clearly, epigenetics has the potential to mediate the actions of chemotherapy on later life physiology and may potentially impact future generations through epigenetic transgenerational inheritance mechanisms, but this needs further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag029"},"PeriodicalIF":4.3,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812184","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}
Samuel Tanner, Katherine Drummond, Sarah Thomson, Kristina Vacy, Christos Symeonides, Boris Novakovic, Toby Mansell, Martin O'Hely, Richard Saffery, Mimi L K Tang, Peter D Sly, Peter Vuillermin, Wah Chin Boon, Chol-Hee Jung, Daniel Park, Anne-Louise Ponsonby
{"title":"Prenatal environmental determinants of aromatase brain-promoter methylation in cord blood: chemical, airborne, pharmacological, and nutritional factors.","authors":"Samuel Tanner, Katherine Drummond, Sarah Thomson, Kristina Vacy, Christos Symeonides, Boris Novakovic, Toby Mansell, Martin O'Hely, Richard Saffery, Mimi L K Tang, Peter D Sly, Peter Vuillermin, Wah Chin Boon, Chol-Hee Jung, Daniel Park, Anne-Louise Ponsonby","doi":"10.1093/eep/dvag027","DOIUrl":"10.1093/eep/dvag027","url":null,"abstract":"<p><p>Aromatase, an enzyme encoded by the gene <i>CYP19A1</i>, plays central roles in neurodevelopment. In the brain, its function is to convert androgens into neuroestrogens, ensuring balanced hormonal signalling. Both animal experiments and human studies have shown that, in males, disruption of aromatase, either genetically or epigenetically, can increase symptoms of autism. Prenatal exposure to bisphenol A (BPA), a common plastic chemical, can increase levels of DNA methylation-a key epigenetic modification-at the brain-specific <i>CYP19A1</i> promoter, P1.f, reducing <i>CYP19A1</i> expression. However, the extent to which other neurodevelopmentally relevant environmental exposures influence P1.f methylation remains unclear. Here, in the Barwon Infant Study (BIS) birth cohort (<i>N</i> = 906), we analysed the association between 25 prenatal exposures (from five classes previously linked to neurodevelopmental outcomes: manufactured chemicals, air pollution, and pharmacological, nutrition and sunlight-related factors) and methylation of the <i>CYP19A1</i> P1.f promoter using Weighted Quantile Sum (WQS) regression. We found that the WQS mixture index, a weighted combination of the prenatal exposures, was positively associated with higher P1.f methylation (Adjusted Mean Difference (AMD) = 0.71 (95% CI 0.11, 1.32), <i>P</i> = 0.021), indicating reduced brain aromatase activity. Prenatal exposures with the strongest contribution to the mixture effect included bisphenols (including BPA), reduced sunlight, household mould, phthalates, low folate intake, and air pollution. These findings highlight epigenetic modification of the aromatase gene as a biologically plausible, convergent mechanism through which multiple environmental risk factors for autism may exert effects.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag027"},"PeriodicalIF":4.3,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857013","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}
Ashley Furtak, Laura Ramos Del Cano, Jeremy Shen, Arthika Bappal, Tony Dadd, Fei Ling Lim, Sheila Rocha, David Gunn
{"title":"Epigenetic changes differentiate between endogenous ageing and photoageing in skin and can detect sun-protection factor cream effects in a 5-month interventional study.","authors":"Ashley Furtak, Laura Ramos Del Cano, Jeremy Shen, Arthika Bappal, Tony Dadd, Fei Ling Lim, Sheila Rocha, David Gunn","doi":"10.1093/eep/dvag025","DOIUrl":"https://doi.org/10.1093/eep/dvag025","url":null,"abstract":"<p><p>Epigenetics is a rapidly expanding field in ageing research. This is partly because changes in DNA methylation are excellent indicators of overall tissue ageing. Here, in a cross-sectional observational study, methylation levels were compared in upper-inner (sun-protected) and lower-outer (sun-exposed) arm skin biopsies of young (21-30 years, <i>n</i> = 24) and older (45-65 years, <i>n</i> = 24) participants of either European or Chinese ancestry. In young sun-protected skin, there were 69 significantly differentially methylated sites (DMSs) between those of Chinese and European ancestry. In a comparison between young and older sun-protected skin (endogenous ageing) there were 3545 pan-ethnic DMSs with a preference for hypermethylation and enrichment at the RNF32, FOXG1, NEFM, and ZIC1 gene loci. For photoageing, 2208 pan-ethnic photoageing DMS were identified with a preference for hypomethylation and enrichment at the HOXB1-3, TWIST1, and TBX20 gene loci. From the photoageing DMSs, 156 CpG sites were selected that consistently differentiated photo-exposed from protected skin even in the young participants. The mean degree of change for these 156 CpG sites was subsequently measured over 5-months in an interventional study on participants' lower outer-arm skin (<i>n</i> = 42). Participants had regular sun-protection factor (SPF) use on one arm and normal free-living conditions on the contralateral arm. The free-living arm demonstrated greater skin darkening and a significantly larger mean change in methylation compared with the SPF-treated arm. Overall, the results highlight endogenous and photoageing methylation differences in skin and suggest that specific DNA methylation sites can track short-term sun-exposure and its attenuation by SPF use.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag025"},"PeriodicalIF":4.3,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180261","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}
Alenka Hafner, Hardik Kundariya, Robersy Sanchez, Akshay U Nair, Sally A Mackenzie
{"title":"Intragenic methylation repatterning is associated with alternative splicing and unique epigenetic phenotypes.","authors":"Alenka Hafner, Hardik Kundariya, Robersy Sanchez, Akshay U Nair, Sally A Mackenzie","doi":"10.1093/eep/dvag026","DOIUrl":"10.1093/eep/dvag026","url":null,"abstract":"<p><p>The role of intragenic cytosine methylation in shaping phenotypes has been contentious. Recent studies show an association between stress and alternative splicing of transcripts, but without functional genome-wide or single-position analysis. We utilized the <i>msh1</i> experimental system in <i>Arabidopsis</i> as a model of reproducible epigenetic states with stress-responsive phenotypes, including commitment to heritable memory for at least seven generations. We mapped the methylome to single-cytosine resolution with signal detection, verified by machine learning. Differentially methylated genes were overlapped with <i>msh1</i>-derived transcript isoforms to show that different patterns of exonic methylation led to different levels of isoform expression. Alternatively spliced and differentially methylated genes were enriched in key regulators of growth and development and spliceosome components. Genes targeted for differential methylation also contained a known CTT motif. These results support an association in plants between environmentally responsive differential methylation and alternative splicing behavior leading to phenotype changes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag026"},"PeriodicalIF":4.3,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13471032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757886","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}
Marilyn N Vera-Chang, John M Danforth, Marilyne Stuart, Marjorie Brand, Aaron A Goodarzi, Richard B Richardson
{"title":"Distinct DNA hydroxymethylation landscape and mitochondrial DNA rearrangement signatures induced by single- and multi-fraction alpha particle radiation in lung fibroblasts.","authors":"Marilyn N Vera-Chang, John M Danforth, Marilyne Stuart, Marjorie Brand, Aaron A Goodarzi, Richard B Richardson","doi":"10.1093/eep/dvag020","DOIUrl":"10.1093/eep/dvag020","url":null,"abstract":"<p><p>Alpha (α)-radiation is a genotoxic and epigenotoxic agent capable of increasing the risk of cancer and other diseases. DNA hydroxymethylation (DNAhm) can modulate gene expression and is considered an under-researched epigenetic event in ionizing radiation studies. Here, the genome-wide DNAhm profile was examined in 64 α-irradiated human embryonic lung fibroblast samples from our 2023 methylome study. These cells were exposed to seven doses (<i>N</i> = 4 per dose) of americium-241 α-particles ranging from 2 to 2200 mGy, using either single-fraction (SF) or multi-fraction (MF) exposure regimens. We report that SF and MF α-irradiation primarily increased DNAhm levels, with a greater number of alterations observed following MF exposure, particularly in gene body regions. Pathway analysis of genes with increased DNAhm levels due to MF exposure suggested disruption of inflammatory responses and other cellular pathways. We also detected DNAhm changes in key genes encoding enzymes involved in DNA methylation (DNAm) and demethylation processes, which support our 2023 DNAm findings. Similar to DNAm, MF α-irradiation induced a greater number of DNAhm changes in aging-associated genes. Compared with equivalent SF doses, MF α-irradiation resulted in more mitochondrial damage. These findings demonstrate that even at comparable doses, SF and MF α-radiation induce radically different effects on the DNAhm and mitochondrial DNA. The DNAhm changes help explain the effects observed in our 2023 methylome study. Altogether, this study supports the idea that environmental radiation exposure regimens are an important consideration when assessing DNAm and DNAhm biomarkers and the potential health effects of α-radiation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"12 1","pages":"dvag020"},"PeriodicalIF":4.3,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577540","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}