Epigenetics Insights最新文献

{"title":"Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer's Disease: Existing Literature and Gaps in Our Understanding.","authors":"Adam Schuller,&nbsp;Luke Montrose","doi":"10.1177/2516865720954873","DOIUrl":"https://doi.org/10.1177/2516865720954873","url":null,"abstract":"<p><p>Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer's disease dementia. Alzheimer's disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer's disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720954873"},"PeriodicalIF":2.2,"publicationDate":"2020-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720954873","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418597","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 Role of DNA Methylation in Transcriptional Regulation of Pro-Nociceptive Genes in Rat Trigeminal Ganglia.","authors":"Guang Bai, Holly Ross, Youping Zhang, KiSeok Lee, Jin Y Ro","doi":"10.1177/2516865720938677","DOIUrl":"10.1177/2516865720938677","url":null,"abstract":"<p><p>Epigenetic modulation by DNA methylation is associated with aberrant gene expression in sensory neurons, which consequently leads to pathological pain responses. In this study, we sought to investigate whether peripheral inflammation alters global DNA methylation in trigeminal ganglia (TG) and results in abnormal expression of pro-nociceptive genes. Our results show that peripheral inflammation remotely reduced the level of global DNA methylation in rat TG with a concurrent reduction in <i>DNMT1</i> and <i>DNMT3a</i> expression. Using unbiased steps, we selected the following pro-nociceptive candidate genes that are potentially regulated by DNA methylation: <i>TRPV1, TRPA1, P2X3</i>, and <i>PIEZO2</i>. Inhibition of DNMT with 5-Aza-dC in dissociated TG cells produced dose-dependent upregulation of <i>TRPV1, TRPA1</i>, and <i>P2X3</i>. Systemic treatment of animals with 5-Aza-dC significantly increased the expression of <i>TRPV1, TRPA1</i>, and <i>PIEZO2</i> in TG. Furthermore, the overexpression of DNMT3a, as delivered by a lentiviral vector, significantly downregulated <i>TRPV1</i> and <i>PIEZO2</i> expression and also reliably decreased <i>TRPA1</i> and <i>P2X3</i> transcripts. MeDIP revealed that this overexpression also significantly enhanced methylation of CGIs associated with <i>TRPV1</i> and <i>TRPA1</i>. In addition, bisulfite sequencing data indicated that the CGI associated with <i>TRPA1</i> was methylated in a pattern catalyzed by DNMT3a. Taken together, our results show that all 4 pro-nociceptive genes are subject to epigenetic modulation via DNA methylation, likely via DNMT3a under inflammatory conditions. These findings provide the first evidence for the functional importance of DNA methylation as an epigenetic factor in the transcription of pro-nociceptive genes in TG that are implicated in pathological orofacial pain responses.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720938677"},"PeriodicalIF":3.6,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38418158","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":"Paternal DNA Methylation May Be Associated With Gestational Age at Birth.","authors":"Rui Luo,&nbsp;Nandini Mukherjee,&nbsp;Su Chen,&nbsp;Yu Jiang,&nbsp;S Hasan Arshad,&nbsp;John W Holloway,&nbsp;Anna Hedman,&nbsp;Olena Gruzieva,&nbsp;Ellika Andolf,&nbsp;Goran Pershagen,&nbsp;Catarina Almqvist,&nbsp;Wilfried Jj Karmaus","doi":"10.1177/2516865720930701","DOIUrl":"https://doi.org/10.1177/2516865720930701","url":null,"abstract":"<p><strong>Background: </strong>How epigenetic modifications of DNA are associated with gestational age at birth is not fully understood. We investigated potential effects of differential paternal DNA methylation (DNAm) on offspring gestational age at birth by conducting an epigenome-wide search for cytosine-phosphate-guanine (CpG) sites.</p><p><strong>Methods: </strong>Study participants in this study consist of male cohort members or partners of the F1-generation of the Isle of Wight Birth Cohort (IoWBC). DNAm levels in peripheral blood from F1-fathers (n = 92) collected around pregnancy of their spouses were analyzed using the Illumina 450K array. A 5-step statistical analysis was performed. First, a training-testing screening approach was applied to select CpG sites that are potentially associated with gestational age at birth. Second, functional enrichment analysis was employed to identify biological processes. Third, by centralizing on biologically informative genes, Cox proportional hazards models were used to assess the hazard ratios of individual paternal CpGs on gestational age adjusting for confounders. Fourth, to assess the validity of our results, we compared our CpG-gestational age correlations within a Born into Life Study in Sweden (n = 15). Finally, we investigated the correlation between the detected CpGs and differential gene expression in F2 cord blood in the IoWBC.</p><p><strong>Results: </strong>Analysis of DNAm of fathers collected around their partner's pregnancy identified 216 CpG sites significantly associated with gestational age at birth. Functional enrichment pathways analyses of the annotated genes revealed 2 biological pathways significantly related to cell-cell membrane adhesion molecules. Differential methylation of 9 cell membrane adhesion pathway-related CpGs were significantly associated with gestational age at birth after adjustment for confounders. The replication sample showed correlation coefficients of 2 pathway-related CpGs with gestational age at birth within 95% confidence intervals of correlation coefficients in IoWBC. Finally, CpG sites of protocadherin (<i>PCDH</i>) gene clusters were associated with gene expression of <i>PCDH</i> in F2 cord blood.</p><p><strong>Conclusions: </strong>Our findings suggest that differential paternal DNAm may affect gestational age at birth through cell-cell membrane adhesion molecules. The results are novel but require future replication in a larger cohort.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720930701"},"PeriodicalIF":2.2,"publicationDate":"2020-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720930701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38411572","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":"An Understudied Dimension: Why Age Needs to Be Considered When Studying Epigenetic-Environment Interactions.","authors":"Rio Barrere-Cain,&nbsp;Patrick Allard","doi":"10.1177/2516865720947014","DOIUrl":"https://doi.org/10.1177/2516865720947014","url":null,"abstract":"<p><p>We live in a complex chemical environment where there are an estimated 350 000 chemical compounds or mixtures commercially produced. A strong body of literature shows that there are time points during early development when an organism's epigenome is particularly sensitive to chemicals in its environment. What is less understood is how gene-environment and epigenetic-environment interactions change with age. This question is bidirectional: (1) how do chemicals in the environment affect the aging process and (2) how does aging affect an organism's response to its chemical environment? The study of gene-environment interactions with age is especially important because, in many parts of the world, older individuals are a large and rapidly growing proportion of the population and because aging is a process universal to most of the animal kingdom. Epigenetics has emerged as a crucial framework for studying aging as epigenetic pathways, often triggered by environmental stimuli, have been shown to be essential regulators of the aging process. In this perspective article, we delineate the connection between aging, epigenetics, and environmental exposures. We discuss why it is essential to consider age when researching how an organism interacts with its environment. We describe recent advances in understanding how the chemical environment affects aging and the gap in research on how age affects an organism's response to the environment. Finally, we highlight how model organisms and network approaches can help fill this crucial gap. Taken together, systemic changes that occur in the epigenome with age indicate that adult organisms cannot be treated as a homogeneous population and that there are discrete mechanisms modulating the aging epigenome that we do not yet understand.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720947014"},"PeriodicalIF":2.2,"publicationDate":"2020-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720947014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38421576","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":"Interweaving Between Genetic and Epigenetic Studies on Childhood Asthma.","authors":"Aniruddha Rathod,&nbsp;Jiasong Duan,&nbsp;Hongmei Zhang,&nbsp;John W Holloway,&nbsp;Susan Ewart,&nbsp;S Hasan Arshad,&nbsp;Wilfried Karmaus","doi":"10.1177/2516865720923395","DOIUrl":"https://doi.org/10.1177/2516865720923395","url":null,"abstract":"<p><p>The cause and underlying mechanisms that contribute to asthma pathogenesis are not well known. Both genome- and epigenome-wide association studies have identified genes associated with asthma risk. It is unknown to what extent genes identified in these two types of studies overlap. Based on existing literature and the DisGeNET database, we extracted overlapping genes identified in genetic and epigenetic studies of childhood asthma. Through analyses of variance, we assessed whether DNA methylation (DNAm) at 5'-C-phosphate-G-3' (CpGs) on the overlapping genes was associated with neighboring single-nucleotide polymorphisms (SNPs) within 1M base pairs (bps) and with low linkage disequilibrium (<i>r</i> ² <i><</i> 0.2) in the childhood asthma-related genes. In total, 285 genes from genetic studies and 226 genes from epigenetic studies were shown to be associated with asthma risk, of which six overlap. Of the six genes, 79 CpGs and 8229 unique neighboring SNPs (1M bps) were included in methylation quantitative loci (methQTL) assessment analyses. We tested the association of DNAm at each of the 79 CpG sites with its neighboring SNPs. After adjusting for multiple testing by controlling the false discovery rate to 0.05 when testing methQTL for each CpG site, we found statistically significant associations in three genes with their neighboring SNPs and identified 34 unique methQTLs. The rather limited overlap in genes between genetic and epigenetic studies on asthma and the absence of methQTL in some of the overlapping genes highlight a need to jointly, rather than independently, examine genetic and epigenetic effects on asthma risk to improve our understanding of the underlying mechanisms of asthma.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720923395"},"PeriodicalIF":2.2,"publicationDate":"2020-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720923395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38228969","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":"Ethical Issues in Research and Development of Epigenome-wide Technologies.","authors":"Eline M Bunnik,&nbsp;Marjolein Timmers,&nbsp;Ineke Lle Bolt","doi":"10.1177/2516865720913253","DOIUrl":"https://doi.org/10.1177/2516865720913253","url":null,"abstract":"<p><p>To date, few scholarly discussions on ethical implications of epigenetics and epigenomics technologies have focused on the current phase of research and development, in which researchers are confronted with real and practical ethical dilemmas. In this article, a responsible research and innovation approach, using interviews and an expert meeting, is applied to a case of epigenomic test development for cervical cancer screening. This article provides an overview of ethical issues presently facing epigenomics researchers and test developers, and discusses 3 sets of issues in depth: (1) informed consent; (2) communication with donors and/or research participants, and (3) privacy and publication of data and research results. Although these issues are familiar to research ethics, some aspects are new and most require reinterpretation in the context of epigenomics technologies. With this article, we aim to start a discussion of the practical ethical issues rising in research and development of epigenomic technologies and to offer guidance for researchers working in the field of epigenetic and epigenomic technology.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720913253"},"PeriodicalIF":2.2,"publicationDate":"2020-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720913253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37853556","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":"Phthalate Exposures and MicroRNA Expression in Uterine Fibroids: The FORGE Study.","authors":"Ami R Zota,&nbsp;Ruth J Geller,&nbsp;Brianna N VanNoy,&nbsp;Cherie Q Marfori,&nbsp;Sana Tabbara,&nbsp;Lisa Y Hu,&nbsp;Andrea A Baccarelli,&nbsp;Gaby N Moawad","doi":"10.1177/2516865720904057","DOIUrl":"https://doi.org/10.1177/2516865720904057","url":null,"abstract":"<p><p>Phthalates are associated with multiple, adverse reproductive outcomes including increased risk of uterine leiomyoma (fibroids). Phthalates can interact with epigenetic modifications including microRNAs (miRNAs), which help regulate processes crucial to fibroid pathogenesis. However, no prior study has examined the influence of phthalates on miRNA expression in fibroid tumors. We conducted a preliminary, cross-sectional study to examine the associations between phthalate exposures and miRNA expression levels in fibroid tumors and to explore potential effect modification by race/ethnicity. We quantified expression levels of 754 miRNAs in fibroid tumor samples and analyzed spot urine samples for phthalate metabolites collected from 45 pre-menopausal women undergoing surgery for fibroid treatment at an academic hospital. Associations between miRNA levels in fibroids and phthalate biomarkers were evaluated using linear regression adjusting for age, race/ethnicity, and body mass index (BMI). Statistical tests were adjusted for multiple comparisons. We also performed in silico Ingenuity Pathway Analysis to identify the biological pathways that are regulated by phthalate-associated miRNAs. Mono-hydroxybutyl phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate were positively associated with miR-10a-5p (β = 0.76, 95% CI = [0.40, 1.11]) and miR-577 (β = 1.06, 95% CI = [0.53, 1.59]), respectively. A total of 8 phthalate-miRNA associations varied by race/ethnicity (q_interaction < 0.10). Pathway analysis revealed that mRNA gene targets of phthalate-associated miRNAs were significantly associated with multiple fibroid-related processes including angiogenesis, apoptosis, and proliferation of connective tissues. Collectively, these data suggest that exposures to some phthalates are associated with miRNA in fibroids, and that associations may vary by race/ethnicity. Validation of these findings may provide insight into mechanisms underlying associations between phthalates and fibroids and contribute to novel hypotheses regarding racial/ethnic disparities in fibroids.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865720904057"},"PeriodicalIF":2.2,"publicationDate":"2020-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720904057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37702970","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":"Three-Dimensional Genome Organization and Virulence in Apicomplexan Parasites.","authors":"Todd Lenz, Karine G Le Roch","doi":"10.1177/2516865719879436","DOIUrl":"10.1177/2516865719879436","url":null,"abstract":"<p><p>Mounting evidence supports the idea that epigenetic, and the overall 3-dimensional (3D) architecture of the genome, plays an important role in gene expression for eukaryotic organisms. We recently used Hi-C methodologies to generate and compare the 3D genome of 7 different apicomplexan parasites, including several pathogenic and less pathogenic malaria parasites as well as related human parasites <i>Babesia microti</i> and <i>Toxoplasma gondii</i>. Our goal was to understand the possible relationship between genome organization, gene expression, and pathogenicity of these infectious agents. Collectively, our results demonstrate that spatial genome organization in most <i>Plasmodium</i> species is constrained by the colocalization of virulence genes that are unique in their effect on chromosome folding, indicating a link between genome organization and gene expression in more virulent pathogens.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865719879436"},"PeriodicalIF":3.2,"publicationDate":"2019-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48424292","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":"Hiding in Plain Sight: Epigenetic Plasticity in Drug-Induced Tumor Evolution","authors":"Ankur Sharma","doi":"10.1177/2516865719870760","DOIUrl":"https://doi.org/10.1177/2516865719870760","url":null,"abstract":"Cancer is a heterogeneous disease with key differences at the cellular and molecular levels. Acquisition of these differences during the course of tumor development manifests into functional and phenotypic heterogeneity leading to tumor diversity, also referred to as intra-tumor heterogeneity (ITH). Within a tumor, there are subpopulations of cells capable of tumor initiation and maintenance. These cells often exhibit resistance to standard-of-care anti-cancer drugs. However, the role of various subpopulations (clones) in drug resistance remains to be investigated. Moreover, the jury is still out about whether drug resistance is a result of clonal selection of preexisting cells, or the cells acquire resistance by dynamic re-wiring of their epigenome. Therefore, we investigated the drug-induced tumor evolution in patient-derived primary cells of head and neck squamous cell carcinoma. Our data demonstrated the role of a preexisting poised epigenetic state in drug-induced adaptive evolution of tumor cells. Importantly, the combination of chemotherapy and epigenetic inhibitors can prevent/delay drug-induced tumor evolution.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719870760","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47604206","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":"Evidence of an Epigenetics System in Archaea","authors":"P. Blum, Sophie Payne","doi":"10.1177/2516865719865280","DOIUrl":"https://doi.org/10.1177/2516865719865280","url":null,"abstract":"Changes in the phenotype of a cell or organism that are heritable but do not involve changes in DNA sequence are referred to as epigenetic. They occur primarily through the gain or loss of chemical modification of chromatin protein or DNA. Epigenetics is therefore a non-Mendelian process. The study of epigenetics in eukaryotes is expanding with advances in knowledge about the relationship between mechanism and phenotype and as a requirement for multicellularity and cancer. However, life also includes other groups or domains, notably the bacteria and archaea. The occurrence of epigenetics in these deep lineages is an emerging topic accompanied by controversy. In these non-eukaryotic organisms, epigenetics is critically important because it stimulates new evolutionary theory and refines perspective about biological action.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719865280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48184763","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}