Epigenetics Insights最新文献

{"title":"Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation.","authors":"Cheyenne A Jones,&nbsp;William P Tansey,&nbsp;April M Weissmiller","doi":"10.1177/25168657221115656","DOIUrl":"https://doi.org/10.1177/25168657221115656","url":null,"abstract":"<p><p>The SWI/SNF chromatin remodeling complex uses the energy of ATP hydrolysis to alter contacts between DNA and nucleosomes, allowing regions of the genome to become accessible for biological processes such as transcription. The SWI/SNF chromatin remodeler is also one of the most frequently altered protein complexes in cancer, with upwards of 20% of all cancers carrying mutations in a SWI/SNF subunit. Intense studies over the last decade have probed the molecular events associated with SWI/SNF dysfunction in cancer and common themes are beginning to emerge in how tumor-associated SWI/SNF mutations promote malignancy. In this review, we summarize current understanding of SWI/SNF complexes, their alterations in cancer, and what is known about the impact of these mutations on tumor-relevant transcriptional events. We discuss how enhancer dysregulation is a common theme in SWI/SNF mutant cancers and describe how resultant alterations in enhancer and super-enhancer activity conspire to block development and differentiation while promoting stemness and self-renewal. We also identify a second emerging theme in which SWI/SNF perturbations intersect with potent oncoprotein transcription factors AP-1 and MYC to drive malignant transcriptional programs.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"15 ","pages":"25168657221115656"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/72/10.1177_25168657221115656.PMC9329810.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9258050","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":"Periconception and Prenatal Exposure to Maternal Perceived Stress and Cord Blood DNA Methylation.","authors":"Kristen J Polinski,&nbsp;Diane L Putnick,&nbsp;Sonia L Robinson,&nbsp;Karen C Schliep,&nbsp;Robert M Silver,&nbsp;Weihua Guan,&nbsp;Enrique F Schisterman,&nbsp;Sunni L Mumford,&nbsp;Edwina H Yeung","doi":"10.1177/25168657221082045","DOIUrl":"https://doi.org/10.1177/25168657221082045","url":null,"abstract":"<p><strong>Background: </strong>Maternal prenatal stress is associated with physiologic and adverse mental health outcomes in the offspring, but the underlying biologic mechanisms are unknown. We examined the associations of maternal perceived stress, including preconception exposure, with DNA methylation (DNAm) alterations in the cord blood buffy coats of 358 singleton infants.</p><p><strong>Methods: </strong>Maternal perceived stress was measured prior to and throughout pregnancy in a cohort of women enrolled in Effects of Aspirin in Gestation and Reproduction Trial (EAGeR) trial. Perceived stress assessments based on a standardized Likert-scale were obtained in periconception (~2 months preconception and 2-8 weeks of gestation) and pregnancy (8-36 weeks of gestation). Cumulative perceived stress was estimated by calculating the predicted area under the curve of stress reported prior to and during pregnancy. DNAm was measured by the Infinium MethylationEPIC BeadChip. Multivariable robust linear regression was used to assess associations of perceived stress with individual CpG probes.</p><p><strong>Results: </strong>Based on a 0 to 3 scale, average reported preconception and early pregnancy stress were 0.76 (0.60) and 0.67 (0.50), respectively. Average mid- to late-pregnancy stress, based on a 0 to 10 scale, was 4.9 (1.6). Neither periconception nor pregnancy perceived stress were associated with individual CpG sites in neonatal cord blood (all false discovery rate [FDR] >5%).</p><p><strong>Conclusion: </strong>No effects of maternal perceived stress exposure on array-wide cord blood neonatal methylation differences were found.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"15 ","pages":"25168657221082045"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/ad/10.1177_25168657221082045.PMC8882928.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10426117","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 Interaction of Trauma Exposure and DNA Methylation on Blood Pressure Among Black Women in the InterGEN Study.","authors":"Billy A Caceres,&nbsp;Yunfeng Huang,&nbsp;Veronica Barcelona,&nbsp;Zeyuan Wang,&nbsp;Kevin P Newhall,&nbsp;Jessica P Cerdeña,&nbsp;Cindy A Crusto,&nbsp;Yan V Sun,&nbsp;Jacquelyn Y Taylor","doi":"10.1177/25168657221138510","DOIUrl":"https://doi.org/10.1177/25168657221138510","url":null,"abstract":"<p><strong>Objective: </strong>Despite evidence that trauma exposure is linked to higher risk of hypertension, epigenetic mechanisms (such as DNA methylation) by which trauma potentially influences hypertension risk among Black adults remain understudied.</p><p><strong>Methods: </strong>Data from a longitudinal study of Black mothers were used to test the hypothesis that direct childhood trauma (ie, personal exposure) and vicarious trauma (ie, childhood trauma experienced by their children) would interact with DNA methylation to increase blood pressure (BP). Separate linear mixed effects models were fitted at each CpG site with the DNA methylation beta-value and direct and vicarious trauma as predictors and systolic and diastolic BP modeled as dependent variables adjusted for age, cigarette smoking, and body mass index. Interaction terms between DNA methylation beta-values with direct and vicarious trauma were added.</p><p><strong>Results: </strong>The sample included 244 Black mothers with a mean age of 31.2 years (SD = ±5.8). Approximately 45% of participants reported at least one form of direct childhood trauma and 49% reported at least one form of vicarious trauma. Epigenome-wide interaction analyses found that no CpG sites passed the epigenome-wide significance level indicating the interaction between direct or vicarious trauma with DNAm did not influence systolic or diastolic BP.</p><p><strong>Conclusions: </strong>This is one of the first studies to simultaneously examine whether direct or vicarious exposure to trauma interact with DNAm to influence BP. Although findings were null, this study highlights directions for future research that investigates epigenetic mechanisms that may link trauma exposure with hypertension risk in Black women.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"15 ","pages":"25168657221138510"},"PeriodicalIF":2.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c5/9c/10.1177_25168657221138510.PMC9716582.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10824719","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":"Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States.","authors":"Jaclyn M Goodrich,&nbsp;Melissa A Furlong,&nbsp;Alberto J Caban-Martinez,&nbsp;Alesia M Jung,&nbsp;Ken Batai,&nbsp;Timothy Jenkins,&nbsp;Shawn Beitel,&nbsp;Sally Littau,&nbsp;John Gulotta,&nbsp;Darin Wallentine,&nbsp;Jeff Hughes,&nbsp;Charles Popp,&nbsp;Miriam M Calkins,&nbsp;Jefferey L Burgess","doi":"10.1177/25168657211006159","DOIUrl":"https://doi.org/10.1177/25168657211006159","url":null,"abstract":"<p><p>Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw <i>P</i>-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (<i>q</i>-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at <i>q</i> < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene <i>SULT1C2</i> had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (<i>FOXK2, GYLTL1B, ZBTB16, ARHGEF10</i>, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"14 ","pages":"25168657211006159"},"PeriodicalIF":2.2,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/25168657211006159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10768648","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":"T. Lenz, K. L. Le Roch","doi":"10.1177/2516865719879436","DOIUrl":"https://doi.org/10.1177/2516865719879436","url":null,"abstract":"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 Babesia microti and Toxoplasma gondii. 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 Plasmodium 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.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719879436","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48424292","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":"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":"Noncatalytic Function of a JmjC Domain Protein Disrupts Heterochromatin","authors":"Kehan Bao, S. Jia","doi":"10.1177/2516865719862249","DOIUrl":"https://doi.org/10.1177/2516865719862249","url":null,"abstract":"Chromatin-modifying enzymes are frequently overexpressed in cancer cells, and their enzymatic activities play important roles in changing the epigenetic landscape responsible for tumorigenesis. However, many of these proteins also execute noncatalytic functions, which are poorly understood. In fission yeast, overexpression of Epe1, a histone demethylase homolog, causes heterochromatin defects. Interestingly, in our recent work, we discovered that overexpressed Epe1 recruits SAGA, a histone acetyltransferase complex important for transcriptional regulation, to disrupt heterochromatin, independent of its demethylase activity. Our findings suggest that overexpressed chromatin-modifying enzymes can alter the epigenetic landscape through changing their proteomic environments, an area that needs to be further explored in dissecting disease etiology associated with overexpression of chromatin regulators.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719862249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49566255","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":"Reviewer List","authors":"","doi":"10.1177/2516865719829636","DOIUrl":"https://doi.org/10.1177/2516865719829636","url":null,"abstract":"","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"12 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865719829636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41851694","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}