Epigenetics Insights最新文献

{"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":"Integrative Analysis of Gene-Specific DNA Methylation and Untargeted Metabolomics Data from the ELEMENT Cohort.","authors":"Jaclyn M Goodrich,&nbsp;Emily C Hector,&nbsp;Lu Tang,&nbsp;Jennifer L LaBarre,&nbsp;Dana C Dolinoy,&nbsp;Adriana Mercado-Garcia,&nbsp;Alejandra Cantoral,&nbsp;Peter Xk Song,&nbsp;Martha Maria Téllez-Rojo,&nbsp;Karen E Peterson","doi":"10.1177/2516865720977888","DOIUrl":"https://doi.org/10.1177/2516865720977888","url":null,"abstract":"<p><p>Epigenetic modifications, such as DNA methylation, influence gene expression and cardiometabolic phenotypes that are manifest in developmental periods in later life, including adolescence. Untargeted metabolomics analysis provide a comprehensive snapshot of physiological processes and metabolism and have been related to DNA methylation in adults, offering insights into the regulatory networks that influence cellular processes. We analyzed the cross-sectional correlation of blood leukocyte DNA methylation with 3758 serum metabolite features (574 of which are identifiable) in 238 children (ages 8-14 years) from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) study. Associations between these features and percent DNA methylation in adolescent blood leukocytes at LINE-1 repetitive elements and genes that regulate early life growth (<i>IGF2, H19, HSD11B2</i>) were assessed by mixed effects models, adjusting for sex, age, and puberty status. After false discovery rate correction (FDR <i>q</i> < 0.05), 76 metabolites were significantly associated with LINE-1 DNA methylation, 27 with <i>HSD11B2</i>, 103 with <i>H19</i>, and 4 with <i>IGF2</i>. The ten identifiable metabolites included dicarboxylic fatty acids (five associated with LINE-1 or <i>H19</i> methylation at <i>q</i> < 0.05) and 1-octadecanoyl-rac-glycerol (<i>q</i> < 0.0001 for association with <i>H19</i> and <i>q</i> = 0.04 for association with LINE-1). We then assessed the association between these ten known metabolites and adiposity 3 years later. Two metabolites, dicarboxylic fatty acid 17:3 and 5-oxo-7-octenoic acid, were inversely associated with measures of adiposity (<i>P</i> < .05) assessed approximately 3 years later in adolescence. In stratified analyses, sex-specific and puberty-stage specific (Tanner stage = 2 to 5 vs Tanner stage = 1) associations were observed. Most notably, hundreds of statistically significant associations were observed between <i>H19</i> and LINE-1 DNA methylation and metabolites among children who had initiated puberty. Understanding relationships between subclinical molecular biomarkers (DNA methylation and metabolites) may increase our understanding of genes and biological pathways contributing to metabolic changes that underlie the development of adiposity during adolescence.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"13 ","pages":"2516865720977888"},"PeriodicalIF":2.2,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865720977888","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358739","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}

{"title":"Stop-and-Go: Dynamics of Nucleolar Transcription During the Cell Cycle.","authors":"Aishwarya Iyer-Bierhoff,&nbsp;Ingrid Grummt","doi":"10.1177/2516865719849090","DOIUrl":"https://doi.org/10.1177/2516865719849090","url":null,"abstract":"Entry into mitosis correlates with nucleolar disassembly and shutdown of ribosomal RNA (rRNA) gene (rDNA) transcription. In telophase, nucleoli reform and transcription is reactivated. The molecular mechanisms underlying the dynamics of nucleolar transcription during the cell cycle are manifold. Although mitotic inactivation of the RNA polymerase I (Pol I) transcription machinery by posttranslational modifications has been extensively studied, little is known about the structure of rDNA chromatin during progression through mitosis. Methylation of histone H2A at glutamine 104 (H2AQ104me), a dedicated nucleolar histone modification, is lost in prometaphase, leading to chromatin compaction, which enforces mitotic repression of rRNA genes. At telophase, restoration of H2AQ104me is required for the activation of transcription. H2AQ104 methylation and chromatin dynamics are regulated by fibrillarin (FBL) and the NAD+-dependent nucleolar deacetylase sirtuin 7 (SIRT7). Deacetylation of FBL is required for the methylation of H2AQ104 and high levels of rDNA transcription during interphase. At the entry into mitosis, nucleoli disassemble and FBL is hyperacetylated, leading to loss of H2AQ104me, chromatin compaction, and shutdown of Pol I transcription. These results reveal that reversible acetylation of FBL regulates methylation of nucleolar H2AQ104, thereby reinforcing oscillation of Pol I transcription during the cell cycle.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865719849090"},"PeriodicalIF":2.2,"publicationDate":"2019-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719849090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37337444","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 Epigenetic Inheritance Is Revealed as a Multi-step Process by Studies of the SET-Domain Proteins SET-25 and SET-32.","authors":"Rachel M Woodhouse,&nbsp;Alyson Ashe","doi":"10.1177/2516865719844214","DOIUrl":"https://doi.org/10.1177/2516865719844214","url":null,"abstract":"<p><p>It is now clear that heredity is not determined purely by Mendelian genetic inheritance; sometimes, epigenetic signals can be passed from parent to progeny for multiple generations. This phenomenon is termed transgenerational epigenetic inheritance (TEI), and examples have now been observed in multiple organisms including plants, flies, mice, and nematodes. Here we discuss the recent findings that TEI is a multi-step process and that the putative chromatin modifiers SET-25 and SET-32 are important in the establishment but not maintenance of silencing.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"2516865719844214"},"PeriodicalIF":2.2,"publicationDate":"2019-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719844214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37182322","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}