Epigenetics最新文献

{"title":"Impact of folic acid supplementation on the epigenetic profile in healthy unfortified individuals – a randomized intervention trial","authors":"Karin B. Michels, Alexandra M. Binder","doi":"10.1080/15592294.2023.2293410","DOIUrl":"https://doi.org/10.1080/15592294.2023.2293410","url":null,"abstract":"Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of...","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"45 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138717085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed immune profiling in pediatric Crohn’s disease using methylation cytometry","authors":"Samuel R. Reynolds, Lucas A. Salas, Ji-Qing Chen, Brock C. Christensen","doi":"10.1080/15592294.2023.2289786","DOIUrl":"https://doi.org/10.1080/15592294.2023.2289786","url":null,"abstract":"DNA methylation has been extensively utilized to study epigenetic patterns across many diseases as well as to deconvolve blood cell type proportions. This study builds upon previous studies examini...","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"1 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory networks of circRNA- centred ceRNAs in sepsis-induced acute kidney injury.","authors":"Tongtong Ma, Junjie Wu, Zhongqing Chen","doi":"10.1080/15592294.2023.2278960","DOIUrl":"10.1080/15592294.2023.2278960","url":null,"abstract":"<p><p>Sepsis is the primary cause of acute kidney injury (AKI) and is associated with high mortality rates. Growing evidence suggests that noncoding RNAs are vitally involved in kidney illnesses, whereas the role of circular RNAs (circRNAs) in sepsis-induced AKI (SAKI) remains largely unknown. In this present study, caecal ligation and puncture (CLP) in mice was performed to establish an SAKI model. The expression of circRNAs and mRNAs was analysed using circRNA microarray or next-generation sequencing. The results revealed that the expressions of 197 circRNAs and 2509 mRNAs were dysregulated. Validation of the selected circRNAs was performed by qRT-PCR. Bioinformatics analyses and chromatin immunoprecipitation demonstrated that NF-κB/p65 signalling induced the upregulation of circC3, circZbtb16, and circFkbp5 and their linear counterparts by p65 transcription in mouse tubular epithelial cells (mTECs). Furthermore, competitive endogenous RNA (ceRNA) networks demonstrated that some components of NF-κB signalling were potential targets of these dysregulated circRNAs. Among them, Tnf-α was increased by circFkbp5 through the downregulation of miR-760-3p in lipopolysaccharide (LPS)-stimulated mTECs. Knocking down circFkbp5 inhibited the p65 phosphorylation and apoptosis in injured mTECs. These findings suggest that the selected circRNAs and the related ceRNA networks provide new knowledge into the fundamental mechanism of SAKI and circFkbp5/miR-760-3p/Tnf-α axis might be therapeutic targets.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2278960"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138046649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel principal component based method for identifying differentially methylated regions in Illumina Infinium MethylationEPIC BeadChip data.","authors":"Yuanchao Zheng, Kathryn L Lunetta, Chunyu Liu, Alicia K Smith, Richard Sherva, Mark W Miller, Mark W Logue","doi":"10.1080/15592294.2023.2207959","DOIUrl":"10.1080/15592294.2023.2207959","url":null,"abstract":"<p><p>Differentially methylated regions (DMRs) are genomic regions with methylation patterns across multiple CpG sites that are associated with a phenotype. In this study, we proposed a Principal Component (PC) based DMR analysis method for use with data generated using the Illumina Infinium MethylationEPIC BeadChip (EPIC) array. We obtained methylation residuals by regressing the M-values of CpGs within a region on covariates, extracted PCs of the residuals, and then combined association information across PCs to obtain regional significance. Simulation-based genome-wide false positive (GFP) rates and true positive rates were estimated under a variety of conditions before determining the final version of our method, which we have named DMR_PC. Then, DMR_PC and another DMR method, coMethDMR, were used to perform epigenome-wide analyses of several phenotypes known to have multiple associated methylation loci (age, sex, and smoking) in a discovery and a replication cohort. Among regions that were analysed by both methods, DMR_PC identified 50% more genome-wide significant age-associated DMRs than coMethDMR. The replication rate for the loci that were identified by only DMR_PC was higher than the rate for those that were identified by only coMethDMR (90% for DMRPC vs. 76% for coMethDMR). Furthermore, DMR_PC identified replicable associations in regions of moderate between-CpG correlation which are typically not analysed by coMethDMR. For the analyses of sex and smoking, the advantage of DMR_PC was less clear. In conclusion, DMR_PC is a new powerful DMR discovery tool that retains power in genomic regions with moderate correlation across CpGs.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2207959"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10193914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-associated DNA methylation changes in <i>Xenopus</i> frogs.","authors":"Marco Morselli, Ronan Bennett, Nikko-Ideen Shaidani, Marko Horb, Leonid Peshkin, Matteo Pellegrini","doi":"10.1080/15592294.2023.2201517","DOIUrl":"10.1080/15592294.2023.2201517","url":null,"abstract":"<p><p>Age-associated changes in DNA methylation have been characterized across various animals, but not yet in amphibians, which are of particular interest because they include widely studied model organisms. In this study, we present clear evidence that the aquatic vertebrate species <i>Xenopus tropicalis</i> displays patterns of age-associated changes in DNA methylation. We have generated whole-genome bisulfite sequencing (WGBS) profiles from skin samples of nine frogs representing young, mature, and old adults and characterized the gene- and chromosome-scale DNA methylation changes with age. Many of the methylation features and changes we observe are consistent with what is known in mammalian species, suggesting that the mechanism of age-related changes is conserved. Moreover, we selected a few thousand age-associated CpG sites to build an assay based on targeted DNA methylation analysis (TBSseq) to expand our findings in future studies involving larger cohorts of individuals. Preliminary results of a pilot TBSeq experiment recapitulate the findings obtained with WGBS setting the basis for the development of an epigenetic clock assay. The results of this study will allow us to leverage the unique resources available for <i>Xenopus</i> to study how DNA methylation relates to other hallmarks of ageing.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2201517"},"PeriodicalIF":2.9,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9706375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the interplay between MeCP2 and histone H1 during <i>in vitro</i> differentiation of human ReNCell neural progenitor cells.","authors":"Edilene Siqueira, Bo-Hyun Kim, Larry Reser, Robert Chow, Kerry Delaney, Manel Esteller, Mark M Ross, Jeffrey Shabanowitz, Donald F Hunt, Sonia Guil, Juan Ausiö","doi":"10.1080/15592294.2023.2276425","DOIUrl":"10.1080/15592294.2023.2276425","url":null,"abstract":"<p><p>An immortalized neural cell line derived from the human ventral mesencephalon, called ReNCell, and its MeCP2 knock out were used. With it, we characterized the chromatin compositional transitions undergone during differentiation, with special emphasis on linker histones. While the WT cells displayed the development of dendrites and axons the KO cells did not, despite undergoing differentiation as monitored by NeuN. ReNCell expressed minimal amounts of histone H1.0 and their linker histone complement consisted mainly of histone H1.2, H1.4 and H1.5. The overall level of histone H1 exhibited a trend to increase during the differentiation of MeCP2 KO cells. The phosphorylation levels of histone H1 proteins decreased dramatically during ReNCell's cell differentiation independently of the presence of MeCP2. Immunofluorescence analysis showed that MeCP2 exhibits an extensive co-localization with linker histones. Interestingly, the average size of the nucleus decreased during differentiation but in the MeCP2 KO cells, the smaller size of the nuclei at the start of differentiation increased by almost 40% after differentiation by 8 days (8 DIV). In summary, our data provide a compelling perspective on the dynamic changes of H1 histones during neural differentiation, coupled with the intricate interplay between H1 variants and MeCP2.<b>Abbreviations</b>: ACN, acetonitrile; A₂₃₀, absorbance at 230 nm; bFGF, basic fibroblast growth factor; CM, chicken erythrocyte histone marker; CNS, central nervous system; CRISPR, clustered regulated interspaced short palindromic repeatsDAPI, 4,'6-diaminidino-2-phenylindole; DIV, days <i>in vitro</i> (days after differentiation is induced); DMEM, Dulbecco's modified Eagle medium; EGF, epidermal growth factor; ESC, embryonic stem cell; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFAP, glial fibrillary acidic proteinHPLC, high-performance liquid chromatography; IF, immunofluorescence; iPSCs, induced pluripotent stem cells; MAP2, microtubule-associated protein 2; MBD, methyl-binding domain; MeCP2, methyl-CpG binding protein 2; MS, mass spectrometry; NCP, nucleosome core particle; NeuN, neuron nuclear antigen; NPC, neural progenitor cellPAGE, polyacrylamide gel electrophoresis; PBS, phosphate buffered saline; PFA, paraformaldehyde; PTM, posttranslational modification; RP-HPLC, reversed phase HPLC; ReNCells, ReNCells VM; RPLP0, ribosomal protein lateral stalk subunit P0; RT-qPCR, reverse transcription quantitative polymerase-chain reaction; RTT, Rett Syndrome; SDS, sodium dodecyl sulphate; TAD, topologically associating domain; Triple KO, triple knockout.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2276425"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10769555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis of epigenome-wide association studies on pregnancy vitamin B12 concentrations and offspring DNA methylation.","authors":"Giulietta S Monasso, Thanh T Hoang, Giulia Mancano, Sílvia Fernández-Barrés, John Dou, Vincent W V Jaddoe, Christian M Page, Laura Johnson, Mariona Bustamante, Kelly M Bakulski, Siri E Håberg, Per M Ueland, Thomas Battram, Simon K Merid, Erik Melén, Doretta Caramaschi, Leanne K Küpers, Jordi Sunyer, Wenche Nystad, Sandra G Heil, Rebecca J Schmidt, Martine Vrijheid, Gemma C Sharp, Stephanie J London, Janine F Felix","doi":"10.1080/15592294.2023.2202835","DOIUrl":"10.1080/15592294.2023.2202835","url":null,"abstract":"<p><p>Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy (<i>n</i> = 2,420) or cord blood (<i>n</i> = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate <i>P</i>-value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood (<i>P</i>_FDR<0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2202835"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10128528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10190570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological stability of DNA methylation measurements over varying intervals of time and in the presence of acute stress.","authors":"Abner T Apsley, Qiaofeng Ye, Laura Etzel, Sarah Wolf, Waylon J Hastings, Brooke C Mattern, Sue Rutherford Siegel, Idan Shalev","doi":"10.1080/15592294.2023.2230686","DOIUrl":"10.1080/15592294.2023.2230686","url":null,"abstract":"<p><p>Identifying factors that influence the stability of DNA methylation measurements across biological replicates is of critical importance in basic and clinical research. Using a within-person between-group experimental design (<i>n</i> = 31, number of observations = 192), we report the stability of biological replicates over a variety of unique temporal scenarios, both in the absence and presence of acute psychosocial stress, and between individuals who have experienced early life adversity (ELA) and non-exposed individuals. We found that varying time intervals, acute stress, and ELA exposure influenced the stability of repeated DNA methylation measurements. In the absence of acute stress, probes were less stable as time passed; however, stress exerted a stabilizing influence on probes over longer time intervals. Compared to non-exposed individuals, ELA-exposed individuals had significantly lower probe stability immediately following acute stress. Additionally, we found that across all scenarios, probes used in most epigenetic-based algorithms for estimating epigenetic age or immune cell proportions had average or below-average stability, except for the Principal Component and DunedinPACE epigenetic ageing clocks, which were enriched for more stable probes. Finally, using highly stable probes in the absence of stress, we identified multiple probes that were hypomethylated in the presence of acute stress, regardless of ELA status. Two hypomethylated probes are located near the transcription start site of the glutathione-disulfide reductase gene (<i>GSR</i>), which has previously been shown to be an integral part of the stress response to environmental toxins. We discuss implications for future studies concerning the reliability and reproducibility of DNA methylation measurements.<b>Abbreviations:</b> DNAm - DNA methylation, CpG - 5'-cytosine-phosphate-guanine-3,' ICC - Interclass correlation coefficient, ELA - Early-life adversity, PBMCs - Peripheral blood mononuclear cells, mQTL - Methylation quantitative trait loci, TSS - Transcription start site, GSR - Glutathione-disulfide reductase gene, TSST - Trier social stress test, PC - Principal component.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2230686"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.","authors":"Wangjin Xu, Weiyang Lou, Linhang Mei","doi":"10.1080/15592294.2022.2148433","DOIUrl":"10.1080/15592294.2022.2148433","url":null,"abstract":"<p><p>Pancreatic adenocarcinoma is one of the leading lethal human cancer types and is notorious for its poor prognosis. A series of bioinformatic analyses and experimental validations were employed to explore the role and mechanism of pseudogene-derived RNAs in pancreatic adenocarcinoma. Consequently, a total of 13 upregulated and 7 downregulated pseudogene-derived RNAs in pancreatic adenocarcinoma were identified. Survival analysis revealed a statistically predictive role of AK4P1 for unfavourable prognosis of patients with pancreatic adenocarcinoma. Subcellular location analysis indicated that AK4P1 was mainly located in cytoplasm, in which AK4P1 might competitively bind to tumour suppressive miR-375 in pancreatic adenocarcinoma. Further analysis showed that SP1 was a potential downstream target gene of miR-375 in pancreatic adenocarcinoma. Intriguingly, expression determination validated that SP1 could positively regulate AK4P1 levels in pancreatic adenocarcinoma. Finally, AK4P1 might also exert its effects by interacting with oncogenic parental gene AK4 in pancreatic adenocarcinoma. Conclusively, the present study elucidated a key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2148433"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9115699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncertainty quantification of reference-based cellular deconvolution algorithms.","authors":"Dorothea Seiler Vellame, Gemma Shireby, Ailsa MacCalman, Emma L Dempster, Joe Burrage, Tyler Gorrie-Stone, Leonard S Schalkwyk, Jonathan Mill, Eilis Hannon","doi":"10.1080/15592294.2022.2137659","DOIUrl":"10.1080/15592294.2022.2137659","url":null,"abstract":"<p><p>The majority of epigenetic epidemiology studies to date have generated genome-wide profiles from bulk tissues (e.g., whole blood) however these are vulnerable to confounding from variation in cellular composition. Proxies for cellular composition can be mathematically derived from the bulk tissue profiles using a deconvolution algorithm; however, there is no method to assess the validity of these estimates for a dataset where the true cellular proportions are unknown. In this study, we describe, validate and characterize a sample level accuracy metric for derived cellular heterogeneity variables. The CETYGO score captures the deviation between a sample's DNA methylation profile and its expected profile given the estimated cellular proportions and cell type reference profiles. We demonstrate that the CETYGO score consistently distinguishes inaccurate and incomplete deconvolutions when applied to reconstructed whole blood profiles. By applying our novel metric to >6,300 empirical whole blood profiles, we find that estimating accurate cellular composition is influenced by both technical and biological variation. In particular, we show that when using a common reference panel for whole blood, less accurate estimates are generated for females, neonates, older individuals and smokers. Our results highlight the utility of a metric to assess the accuracy of cellular deconvolution, and describe how it can enhance studies of DNA methylation that are reliant on statistical proxies for cellular heterogeneity. To facilitate incorporating our methodology into existing pipelines, we have made it freely available as an R package (https://github.com/ds420/CETYGO).</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"18 1","pages":"2137659"},"PeriodicalIF":3.7,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9117164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}