Epigenetics Insights最新文献

{"title":"Stress Overload and DNA Methylation in African American Women in the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure Study.","authors":"Jolaade Kalinowski,&nbsp;Yunfeng Huang,&nbsp;Martin A Rivas,&nbsp;Veronica Barcelona,&nbsp;Michelle L Wright,&nbsp;Cindy Crusto,&nbsp;Tanya Spruill,&nbsp;Yan V Sun,&nbsp;Jacquelyn Y Taylor","doi":"10.1177/25168657221126314","DOIUrl":"https://doi.org/10.1177/25168657221126314","url":null,"abstract":"<p><strong>Introduction: </strong>Experiencing psychosocial stress is associated with poor health outcomes such as hypertension and obesity, which are risk factors for developing cardiovascular disease. African American women experience disproportionate risk for cardiovascular disease including exposure to high levels of psychosocial stress. We hypothesized that psychosocial stress, such as perceived stress overload, may influence epigenetic marks, specifically DNA methylation (DNAm), that contribute to increased risk for cardiovascular disease in African American women.</p><p><strong>Methods: </strong>We conducted an epigenome-wide study evaluating the relationship of psychosocial stress and DNAm among African American mothers from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) cohort. Linear mixed effects models were used to explore the epigenome-wide associations with the Stress Overload Scale (SOS), which examines self-reported past-week stress, event load and personal vulnerability.</p><p><strong>Results: </strong>In total, n = 228 participants were included in our analysis. After adjusting for known epigenetic confounders, we did not identify any DNAm sites associated with maternal report of stress measured by SOS after controlling for multiple comparisons. Several of the top differentially methylated CpG sites related to SOS score (<i>P</i> < 1 × 10^-5), mapped to genes of unknown significance for hypertension or heart disease, namely, <i>PXDNL</i> and <i>C22orf42</i>.</p><p><strong>Conclusions: </strong>This study provides foundational knowledge for future studies examining epigenetic associations with stress and other psychosocial measures in African Americans, a key area for growth in epigenetics. Future studies including larger sample sizes and replication data are warranted.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657221126314"},"PeriodicalIF":2.2,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/31/10.1177_25168657221126314.PMC9554129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33516011","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":"HP1-Driven Micro-Phase Separation of Heterochromatin-Like Domains/Complexes.","authors":"Prim B Singh,&nbsp;Andrew G Newman","doi":"10.1177/25168657221109766","DOIUrl":"https://doi.org/10.1177/25168657221109766","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Cytologically visible constitutive heterochromatin found at the centromeric and telomeric regions of chromosomes represents the largest differentiated chromatin compartment in eukaryotic nuclei.1 Outside constitutive heterochromatin, heterochromatin-like domains (HLD, >.1 Mb) and complexes (HLC, <.1 Mb) are found along the chromosome arms.2 HLD/Cs are present in eukaryotic genomes as divergent as fission yeast and human, with expansions in size and number in mammals. In human, there are ~163 to 859 HLDs and ~18 853 to 32 292 HLCs, depending on cell type.2 Some of the largest HLDs are the KRAB-ZNF HLDs on chromosome 19. Notably, contacts among these large HLDs emerge as the heterochromatic B4 sub-compartment in Hi-C maps.3 Both cytologically visible constitutive heterochromatin and HLD/Cs are associated with the di/tri-methyl modification of lysine 9 on histone H3 (H3K9me2/3) and the HP1-class of chromodomain (CD) proteins.1,2 The HP1 CD binds to H3K9me2/3 and HP1 proteins dimerise through the chromo shadow domain (CSD), creating ‘bridges’ between 2 H3K9methylated molecules in separate nucleosomes.4 How the HP1 and H3K9me2/3-marked chromatin are involved in partitioning the genome into cytologically visible constitutive heterochromatin and euchromatin as well as into the heterochromatic B-type and euchromatic A-type compartments has been the subject of intense research and led to the notion that the partitioning observed is driven by the same physiochemical process, namely phase separation. However, recent work shows that HP1-driven liquid-liquid phase separation (LLPS) is unlikely to play a major role in the formation and establishment of constitutive heterochromatin. By contrast, HP1 proteins appear to be key players in micro-phase separation and segregation of HLD/ Cs that generate heterochromatic B-type compartments.","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657221109766"},"PeriodicalIF":2.2,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9b/da/10.1177_25168657221109766.PMC9260563.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40490380","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":"Regulation of mi-RNAs Target Cancer Genes Between Exercise and Non-exercise in Rat Rheumatoid Arthritis Induction: Pilot Study.","authors":"Vimolmas Tansathitaya,&nbsp;Witchana Sarasin,&nbsp;Tanapati Phakham,&nbsp;Vorthon Sawaswong,&nbsp;Prangwalai Chanchaem,&nbsp;Sunchai Payungporn","doi":"10.1177/25168657221110485","DOIUrl":"https://doi.org/10.1177/25168657221110485","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis is associated with various cancers. Many studies have investigated physical exercise interventions as health improvements to ameliorate the risk of cancer during rheumatoid arthritis diagnosis. Recently, microRNAs were used as biomarkers for health assessment and cancer prediction in rheumatoid arthritis patients.</p><p><strong>Methods: </strong>The effects of exercise interventions on serum microRNAs were investigated in pristane-induced arthritis (PIA) rat models. Twelve Sprague-Dawley male rats were divided into 4 groups including non-exercise without PIA (N-EX), non-exercise with PIA (N-EX + PIA), exercise without PIA (EX) and exercise with PIA (EX + PIA). Blood samples were collected at the end of the study period to analyze miRNA biomarkers and target cancer gene predictions.</p><p><strong>Results: </strong>Four significant Rattus norvegicus (rno-microRNAs) may purpose as tumor suppressors were identified as potential target cancer gene candidate expressions within the 4 comparative interventional exercise groups. One rno-microRNA and target cancer gene candidate was up-regulated and 3 rno-microRNAs and their target cancer genes were down-regulated.</p><p><strong>Conclusions: </strong>Exercise interventions affected rno-miRNAs regulated target cancer gene candidates ITPR3, SOCS6, ITGA6, and NKX2-1 as biomarkers for cancer prognosis in rheumatoid arthritis diagnosis.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657221110485"},"PeriodicalIF":2.2,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/29/10.1177_25168657221110485.PMC9253985.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40569598","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":"Associations Between DNA Methylation Age Acceleration, Depressive Symptoms, and Cardiometabolic Traits in African American Mothers From the InterGEN Study.","authors":"Nicole Beaulieu Perez, Allison A Vorderstrasse, Gary Yu, Gail D'Eramo Melkus, Fay Wright, Stephen D Ginsberg, Cindy A Crusto, Yan V Sun, Jacquelyn Y Taylor","doi":"10.1177/25168657221109781","DOIUrl":"10.1177/25168657221109781","url":null,"abstract":"<p><strong>Background: </strong>African American women (AAW) have a high risk of both cardiometabolic (CM) illness and depressive symptoms. Depressive symptoms co-occur in individuals with CM illness at higher rates than the general population, and accelerated aging may explain this. In this secondary analysis, we examined associations between age acceleration; depressive symptoms; and CM traits (hypertension, diabetes mellitus [DM], and obesity) in a cohort of AAW.</p><p><strong>Methods: </strong>Genomic and clinical data from the InterGEN cohort (n = 227) were used. Age acceleration was based on the Horvath method of DNA methylation (DNAm) age estimation. Accordingly, DNAm age acceleration (DNAm AA) was defined as the residuals from a linear regression of DNAm age on chronological age. Spearman's correlations, linear and logistic regression examined associations between DNAm AA, depressive symptoms, and CM traits.</p><p><strong>Results: </strong>DNAm AA did not associate with total depressive symptom scores. DNAm AA correlated with specific symptoms including self-disgust/self-hate (-0.13, 95% CI -0.26, -0.01); difficulty with making decisions (-0.15, 95% CI -0.28, -0.02); and worry over physical health (0.15, 95% CI 0.02, 0.28), but were not statistically significant after multiple comparison correction. DNAm AA associated with obesity (0.08, 95% CI 1.02, 1.16), hypertension (0.08, 95% CI 1.01, 1.17), and DM (0.20, 95% CI 1.09, 1.40), after adjustment for potential confounders.</p><p><strong>Conclusions: </strong>Associations between age acceleration and depressive symptoms may be highly nuanced and dependent on study design contexts. Factors other than age acceleration may explain the connection between depressive symptoms and CM traits. AAW with CM traits may be at increased risk of accelerated aging.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":"15 ","pages":"25168657221109781"},"PeriodicalIF":3.2,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a0/cd/10.1177_25168657221109781.PMC9247996.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10346711","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":"Roles of Wnt Signaling Pathway and ROR2 Receptor in Embryonic Development: An Update Review Article.","authors":"Rui Guo,&nbsp;Quan Sheng Xing","doi":"10.1177/25168657211064232","DOIUrl":"https://doi.org/10.1177/25168657211064232","url":null,"abstract":"<p><p>The Wnt family is a large class of highly conserved cysteine-rich secretory glycoproteins that play a vital role in various cellular and physiological courses through different signaling pathways during embryogenesis and tissue homeostasis 3. Wnt5a is a secreted glycoprotein that belongs to the noncanonical Wnt family and is involved in a wide range of developmental and tissue homeostasis. A growing body of evidence suggests that Wnt5a affects embryonic development, signaling through various receptors, starting with the activation of β-catenin by Wnt5a. In addition to affecting planar cell polarity and Ca²⁺ pathways, β-catenin also includes multiple signaling cascades that regulate various cell functions. Secondly, Wnt5a can bind to Ror receptors to mediate noncanonical Wnt signaling and a significant ligand for Ror2 in vertebrates. Consistent with the multiple functions of Wnt5A/Ror2 signaling, Wnt5A knockout mice exhibited various phenotypic defects, including an inability to extend the anterior and posterior axes of the embryo. Numerous essential roles of Wnt5a/Ror2 in development have been demonstrated. Therefore, Ror signaling pathway become a necessary target for diagnosing and treating human diseases. The Wnt5a- Ror2 signaling pathway as a critical factor has attracted extensive attention.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211064232"},"PeriodicalIF":2.2,"publicationDate":"2022-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/9f/10.1177_25168657211064232.PMC8808015.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39592789","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":"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":"Exploring the Ethics of Implementation of Epigenomics Technologies in Cancer Screening: A Focus Group Study.","authors":"Eline M Bunnik,&nbsp;Ineke Lle Bolt","doi":"10.1177/25168657211063618","DOIUrl":"https://doi.org/10.1177/25168657211063618","url":null,"abstract":"<p><p>New epigenomics technologies are being developed and used for the detection and prediction of various types of cancer. By allowing for timely intervention or preventive measures, epigenomics technologies show promise for public health, notably in population screening. In order to assess whether implementation of epigenomics technologies in population screening may be morally acceptable, it is important to understand - in an early stage of development - ethical and societal issues that may arise. We held 3 focus groups with experts in science and technology studies (STS) (n = 13) in the Netherlands, on 3 potential future applications of epigenomic technologies in screening programmes of increasing scope: cervical cancer, female cancers and 'global' cancer. On the basis of these discussions, this paper identifies ethical issues pertinent to epigenomics-based population screening, such as risk communication, trust and public acceptance; personal responsibility, stigmatisation and societal pressure, and data protection and data governance. It also points out how features of epigenomics (eg, modifiability) and changing concepts (eg, of cancer) may challenge the existing evaluative framework for screening programmes. This paper aims to anticipate and prepare for future ethical challenges when epigenomics technologies can be tested and introduced in public health settings.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211063618"},"PeriodicalIF":2.2,"publicationDate":"2021-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8669112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39822233","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":"Global Histone H3 Lysine 4 Trimethylation (H3K4me3) Landscape Changes in Response to TGFβ.","authors":"Ankit Naik,&nbsp;Nidhi Dalpatraj,&nbsp;Noopur Thakur","doi":"10.1177/25168657211051755","DOIUrl":"https://doi.org/10.1177/25168657211051755","url":null,"abstract":"<p><p>TGFβ expression acts as a biomarker of poor prognosis in prostate cancer. It plays a dual functional role in prostate cancer. In the early stages of the tumor, it acts as a tumor suppressor while at the later stages of tumor development, it promotes metastasis. The molecular mechanisms of action of TGFβ are largely understood through the canonical and non-canonical signal transduction pathways. Our understanding of the mechanisms that establish transient TGFβ stimulation into stable gene expression patterns remains incomplete. Epigenetic marks like histone H3 modifications are directly linked with gene expression and they play an important role in tumorigenesis. In this report, we performed chromatin immunoprecipitation-sequencing (ChIP-Seq) to identify the genome-wide regions that undergo changes in histone H3 Lysine 4 trimethylation (H3K4me3) occupancy in response to TGFβ stimulation. We also show that TGFβ stimulation can induce acute epigenetic changes through the modulation of H3K4me3 signals at genes belonging to special functional categories in prostate cancer. TGFβ induces the H3K4me3 on its own ligands like TGFβ, GDF1, INHBB, GDF3, GDF6, BMP5 suggesting a positive feedback loop. The majority of genes were found to be involved in the positive regulation of transcription from the RNA polymerase II promoter in response to TGFβ. Other functional categories were intracellular protein transport, brain development, EMT, angiogenesis, antigen processing, antigen presentation via MHC class II, lipid transport, embryo development, histone H4 acetylation, positive regulation of cell cycle arrest, and genes involved in mitotic G2 DNA damage checkpoints. Our results link TGFβ stimulation to acute changes in gene expression through an epigenetic mechanism. These findings have broader implications on epigenetic bases of acute gene expression changes caused by growth factor stimulation.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":" ","pages":"25168657211051755"},"PeriodicalIF":2.2,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e3/e3/10.1177_25168657211051755.PMC8521735.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39535652","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}