Environmental Epigenetics最新文献

{"title":"Epigenetic and gene therapy in human and veterinary medicine.","authors":"Eva Bártová","doi":"10.1093/eep/dvae006","DOIUrl":"10.1093/eep/dvae006","url":null,"abstract":"<p><p>Gene therapy is a focus of interest in both human and veterinary medicine, especially in recent years due to the potential applications of CRISPR/Cas9 technology. Another relatively new approach is that of epigenetic therapy, which involves an intervention based on epigenetic marks, including DNA methylation, histone post-translational modifications, and post-transcription modifications of distinct RNAs. The epigenome results from enzymatic reactions, which regulate gene expression without altering DNA sequences. In contrast to conventional CRISP/Cas9 techniques, the recently established methodology of epigenetic editing mediated by the CRISPR/dCas9 system is designed to target specific genes without causing DNA breaks. Both natural epigenetic processes and epigenetic editing regulate gene expression and thereby contribute to maintaining the balance between physiological functions and pathophysiological states. From this perspective, knowledge of specific epigenetic marks has immense potential in both human and veterinary medicine. For instance, the use of epigenetic drugs (chemical compounds with therapeutic potential affecting the epigenome) seems to be promising for the treatment of cancer, metabolic, and infectious diseases. Also, there is evidence that an epigenetic diet (nutrition-like factors affecting epigenome) should be considered as part of a healthy lifestyle and could contribute to the prevention of pathophysiological processes. In summary, epigenetic-based approaches in human and veterinary medicine have increasing significance in targeting aberrant gene expression associated with various diseases. In this case, CRISPR/dCas9, epigenetic targeting, and some epigenetic nutrition factors could contribute to reversing an abnormal epigenetic landscape to a healthy physiological state.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae006"},"PeriodicalIF":3.8,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944540","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":"Accelerated aging and altered subclinical response to ozone exposure in young, healthy adults.","authors":"William C Weston, Marie Abèle Bind, Wayne E Cascio, Robert B Devlin, David Diaz-Sanchez, Cavin K Ward-Caviness","doi":"10.1093/eep/dvae007","DOIUrl":"10.1093/eep/dvae007","url":null,"abstract":"<p><p>Ozone exposure induces a myriad of adverse cardiopulmonary outcomes in humans. Although advanced age and chronic disease are factors that may exacerbate a person's negative response to ozone exposure, there are no molecular biomarkers of susceptibility. Here, we examine whether epigenetic age acceleration (EAA) is associated with responsiveness to short-term ozone exposure. Using data from a crossover-controlled exposure study (<i>n</i> = 17), we examined whether EAA, as measured in lung epithelial cells collected 24 h after clean air exposure, modifies the observed effect of ozone on autonomic function, cardiac electrophysiology, hemostasis, pulmonary function, and inflammation. EAA was assessed in lung epithelial cells extracted from bronchoalveolar lavage fluids, using the pan-tissue aging clock. We used two analytic approaches: (i) median regression to estimate the association between EAA and the estimated risk difference for subclinical responses to ozone and (ii) a block randomization approach to estimate EAA's effect modification of subclinical responses. For both approaches, we calculated Fisher-exact <i>P</i>-values, allowing us to bypass large sample size assumptions. In median regression analyses, accelerated epigenetic age modified associations between ozone and heart rate-corrected QT interval (QTc) ([Formula: see text]= 0.12, <i>P</i>-value = 0.007) and between ozone and C-reactive protein ([Formula: see text] = -0.18, <i>P</i> = 0.069). During block randomization, the directions of association remained consistent for QTc and C-reactive protein; however, the <i>P</i>-values weakened. Block randomization also revealed that responsiveness of plasminogen activator inhibitor-1 (PAI-1) to ozone exposure was modified by accelerated epigenetic aging (PAI-1 difference between accelerated aging-defined block groups = -0.54, <i>P</i>-value = 0.039). In conclusion, EAA is a potential biomarker for individuals with increased susceptibility to ozone exposure even among young, healthy adults.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae007"},"PeriodicalIF":3.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283292","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":"Symposium summary: epigenetic inheritance-impact for biology and society 23-25 August 2023, Zürich, Switzerland.","authors":"Leonard C Steg, Ellen Jaspers, Anar Alshanbayeva, Rodrigo G Arzate-Meija, Maria A Dimitriu, Katharina Gapp, Lola M Kourouma, Kerem Uzel, Isabelle M Mansuy","doi":"10.1093/eep/dvae002","DOIUrl":"https://doi.org/10.1093/eep/dvae002","url":null,"abstract":"<p><p>The possibility that acquired traits can be transmitted across generations has been the subject of intense research in the past decades. This biological process is of major interest to many scientists and has profound implications for biology and society but has complex mechanisms and is therefore challenging to study. Because it involves factors independent from the DNA sequence, this form of heredity is classically referred to as epigenetic inheritance. Many studies have examined how life experiences and various environmental factors can cause phenotypes that are heritable and be manifested in subsequent generations. Recognizing the major importance and complexity of this research, the fourth edition of the Epigenetic Inheritance Symposium Zürich brought together experts from diverse disciplines to address current questions in the field of epigenetic inheritance and present recent findings. The symposium had sessions dedicated to epidemiological evidence and animal models, transmission mechanisms, methodologies and the far-reaching impact on society and evolution. This report summarizes the talks of speakers and describes additional activities offered during the symposium including poster sessions and an art competition on the topic of epigenetic inheritance.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"10 1","pages":"dvae002"},"PeriodicalIF":3.8,"publicationDate":"2024-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143035","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":"Characterization of genomic regions escaping epigenetic reprogramming in sheep","authors":"C. U. Braz, M. Passamonti, Hasan Khatib","doi":"10.1093/eep/dvad010","DOIUrl":"https://doi.org/10.1093/eep/dvad010","url":null,"abstract":"\u0000 The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the preimplantation embryo after fertilization. These events involve the erasure and reestablishment of DNA methylation marks. However, imprinted genes and transposable elements maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species. Therefore, the objective of this study was to examine the characteristics and locations of genomic regions that evade epigenetic reprogramming in sheep, as well as to explore the biological functions of the genes within these regions. In a previous study, we identified 107 transgenerationally inherited differentially methylated cytosines (DMCs) in the F1 and F2 generations in response to a paternal methionine-supplemented diet. These DMCs were found in transposable elements, non-repetitive regions, imprinted and non-imprinted genes. Our findings suggest that genomic regions, rather than transposable elements and imprinted genes, have the propensity to escape reprogramming and serve as potential candidates for transgenerational epigenetic inheritance. Notably, 34 transgenerational methylated genes influenced by paternal nutrition escaped reprogramming, impacting growth, development, male fertility, cardiac disorders, and neurodevelopment. Intriguingly, among these genes, 21 have been associated with neural development and brain disorders, such as autism, schizophrenia, bipolar disease, and intellectual disability. This suggests a potential genetic overlap between brain and infertility disorders. Overall, our study supports the concept of transgenerational epigenetic inheritance of environmentally induced marks in mammals.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"28 17","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138955245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple generation distinct toxicant exposures induce epigenetic transgenerational inheritance of enhanced pathology and obesity.","authors":"Eric E Nilsson, Margaux McBirney, Sarah De Santos, Stephanie E King, Daniel Beck, Colin Greeley, Lawrence B Holder, Michael K Skinner","doi":"10.1093/eep/dvad006","DOIUrl":"10.1093/eep/dvad006","url":null,"abstract":"<p><p>Three successive multiple generations of rats were exposed to different toxicants and then bred to the transgenerational F5 generation to assess the impacts of multiple generation different exposures. The current study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide dichlorodiphenyltrichloroethane on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational generation were obtained and F1-F5 generations examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions were observed. The F3-F5 generations were similar in ∼50% of the DNA methylation regions. The pathology of each generation was assessed in the testis, ovary, kidney, and prostate, as well as the presence of obesity and tumors. The pathology used a newly developed Deep Learning, artificial intelligence-based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Observations demonstrate that multiple generational exposures, which occur in human populations, appear to increase epigenetic impacts and disease susceptibility.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad006"},"PeriodicalIF":3.8,"publicationDate":"2023-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10756336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073667","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":"Identifying unique exposure-specific transgenerational differentially DNA methylated region epimutations in the genome using hybrid deep learning prediction models.","authors":"Pegah Mavaie, Lawrence Holder, Michael Skinner","doi":"10.1093/eep/dvad007","DOIUrl":"10.1093/eep/dvad007","url":null,"abstract":"<p><p>Exposure to environmental toxicants can lead to epimutations in the genome and an increase in differential DNA methylated regions (DMRs) that have been linked to increased susceptibility to various diseases. However, the unique effect of particular toxicants on the genome in terms of leading to unique DMRs for the toxicants has been less studied. One hurdle to such studies is the low number of observed DMRs per toxicants. To address this hurdle, a previously validated hybrid deep-learning cross-exposure prediction model is trained per exposure and used to predict exposure-specific DMRs in the genome. Given these predicted exposure-specific DMRs, a set of unique DMRs per exposure can be identified. Analysis of these unique DMRs through visualization, DNA sequence motif matching, and gene association reveals known and unknown links between individual exposures and their unique effects on the genome. The results indicate the potential ability to define exposure-specific epigenetic markers in the genome and the potential relative impact of different exposures. Therefore, a computational approach to predict exposure-specific transgenerational epimutations was developed, which supported the exposure specificity of ancestral toxicant actions and provided epigenome information on the DMR sites predicted.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad007"},"PeriodicalIF":3.8,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10735314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828841","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":"Inheritance of environment-induced phenotypic changes through epigenetic mechanisms.","authors":"Yukiko Tando, Yasuhisa Matsui","doi":"10.1093/eep/dvad008","DOIUrl":"10.1093/eep/dvad008","url":null,"abstract":"<p><p>Growing evidence suggests that epigenetic changes through various parental environmental factors alter the phenotypes of descendants in various organisms. Environmental factors, including exposure to chemicals, stress and abnormal nutrition, affect the epigenome in parental germ cells by different epigenetic mechanisms, such as DNA methylation, histone modification as well as small RNAs via metabolites. Some current remaining questions are the causal relationship between environment-induced epigenetic changes in germ cells and altered phenotypes of descendants, and the molecular basis of how the abnormal epigenetic changes escape reprogramming in germ cells. In this review, we introduce representative examples of intergenerational and transgenerational inheritance of phenotypic changes through parental environmental factors and the accompanied epigenetic and metabolic changes, with a focus on animal species. We also discuss the molecular mechanisms of epigenomic inheritance and their possible biological significance.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad008"},"PeriodicalIF":3.8,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797520","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 clocks and research implications of the lack of data on whom they have been developed: a review of reported and missing sociodemographic characteristics.","authors":"Sarah Holmes Watkins, Christian Testa, Jarvis T Chen, Immaculata De Vivo, Andrew J Simpkin, Kate Tilling, Ana V Diez Roux, George Davey Smith, Pamela D Waterman, Matthew Suderman, Caroline Relton, Nancy Krieger","doi":"10.1093/eep/dvad005","DOIUrl":"10.1093/eep/dvad005","url":null,"abstract":"<p><p>Epigenetic clocks are increasingly being used as a tool to assess the impact of a wide variety of phenotypes and exposures on healthy ageing, with a recent focus on social determinants of health. However, little attention has been paid to the sociodemographic characteristics of participants on whom these clocks have been based. Participant characteristics are important because sociodemographic and socioeconomic factors are known to be associated with both DNA methylation variation and healthy ageing. It is also well known that machine learning algorithms have the potential to exacerbate health inequities through the use of unrepresentative samples - prediction models may underperform in social groups that were poorly represented in the training data used to construct the model. To address this gap in the literature, we conducted a review of the sociodemographic characteristics of the participants whose data were used to construct 13 commonly used epigenetic clocks. We found that although some of the epigenetic clocks were created utilizing data provided by individuals from different ages, sexes/genders, and racialized groups, sociodemographic characteristics are generally poorly reported. Reported information is limited by inadequate conceptualization of the social dimensions and exposure implications of gender and racialized inequality, and socioeconomic data are infrequently reported. It is important for future work to ensure clear reporting of tangible data on the sociodemographic and socioeconomic characteristics of all the participants in the study to ensure that other researchers can make informed judgements about the appropriateness of the model for their study population.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad005"},"PeriodicalIF":4.8,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10411856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547124","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 sperm DMRs escape DNA methylation erasure during embryonic development and epigenetic inheritance.","authors":"Millissia Ben Maamar, Yue Wang, Eric E Nilsson, Daniel Beck, Wei Yan, Michael K Skinner","doi":"10.1093/eep/dvad003","DOIUrl":"10.1093/eep/dvad003","url":null,"abstract":"<p><p>Germline transmission of epigenetic information is a critical component of epigenetic inheritance. Previous studies have suggested that an erasure of DNA methylation is required to develop stem cells in the morula embryo. An exception involves imprinted genes that escape this DNA methylation erasure. Transgenerational differential DNA methylation regions (DMRs) have been speculated to be imprinted-like and escape this erasure. The current study was designed to assess if morula embryos escape the erasure of dichlorodiphenyltrichloroethane-induced transgenerational sperm DMR methylation. Observations demonstrate that the majority (98%) of transgenerational sperm DMR sites retain DNA methylation and are not erased, so appearing similar to imprinted-like sites. Interestingly, observations also demonstrate that the majority of low-density CpG genomic sites had a significant increase in DNA methylation in the morula embryo compared to sperm. This is in contrast to the previously observed DNA methylation erasure of higher-density CpG sites. The general erasure of DNA methylation during embryogenesis appears applicable to high-density DNA methylation sites (e.g. CpG islands) but neither to transgenerational DMR methylation sites nor to low-density CpG deserts, which constitute the vast majority of the genome's DNA methylation sites. The role of epigenetics during embryogenesis appears more dynamic than the simple erasure of DNA methylation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad003"},"PeriodicalIF":3.8,"publicationDate":"2023-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/1a/dvad003.PMC10281242.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9702598","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":"Context-dependent DNA methylation signatures in animal livestock.","authors":"Geetha Venkatesh, Sina Tönges, Katharina Hanna, Yi Long Ng, Rose Whelan, Ranja Andriantsoa, Annika Lingenberg, Suki Roy, Sanjanaa Nagarajan, Steven Fong, Günter Raddatz, Florian Böhl, Frank Lyko","doi":"10.1093/eep/dvad001","DOIUrl":"10.1093/eep/dvad001","url":null,"abstract":"<p><p>DNA methylation is an important epigenetic modification that is widely conserved across animal genomes. It is widely accepted that DNA methylation patterns can change in a context-dependent manner, including in response to changing environmental parameters. However, this phenomenon has not been analyzed in animal livestock yet, where it holds major potential for biomarker development. Building on the previous identification of population-specific DNA methylation in clonal marbled crayfish, we have now generated numerous base-resolution methylomes to analyze location-specific DNA methylation patterns. We also describe the time-dependent conversion of epigenetic signatures upon transfer from one environment to another. We further demonstrate production system-specific methylation signatures in shrimp, river-specific signatures in salmon and farm-specific signatures in chicken. Together, our findings provide a detailed resource for epigenetic variation in animal livestock and suggest the possibility for origin tracing of animal products by epigenetic fingerprinting.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"9 1","pages":"dvad001"},"PeriodicalIF":3.8,"publicationDate":"2023-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/1f/dvad001.PMC10019019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9145699","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}