Epigenomes最新文献

{"title":"Excessive Gestational Weight Gain Alters DNA Methylation and Influences Foetal and Neonatal Body Composition.","authors":"Perla Pizzi Argentato,&nbsp;João Victor da Silva Guerra,&nbsp;Liania Alves Luzia,&nbsp;Ester Silveira Ramos,&nbsp;Mariana Maschietto,&nbsp;Patrícia Helen de Carvalho Rondó","doi":"10.3390/epigenomes7030018","DOIUrl":"https://doi.org/10.3390/epigenomes7030018","url":null,"abstract":"<p><strong>Background: </strong>Changes in body weight are associated with the regulation of DNA methylation (DNAm). In this study, we investigated the associations between maternal gestational weight gain-related DNAm and foetal and neonatal body composition.</p><p><strong>Methods: </strong>Brazilian pregnant women from the Araraquara Cohort Study were followed up during pregnancy, delivery, and after hospital discharge. Women with normal pre-pregnancy BMI were allocated into two groups: adequate gestational weight gain (AGWG, <i>n</i> = 45) and excessive gestational weight gain (EGWG, <i>n</i> = 30). Foetal and neonatal body composition was evaluated via ultrasound and plethysmography, respectively. DNAm was assessed in maternal blood using Illumina Infinium MethylationEPIC BeadChip arrays. Linear regression models were used to explore the associations between DNAm and foetal and neonatal body composition.</p><p><strong>Results: </strong>Maternal weight, GWG, neonatal weight, and fat mass were higher in the EGWG group. Analysis of DNAm identified 46 differentially methylated positions and 11 differentially methylated regions (DMRs) between the EGWG and AGWG groups. Nine human phenotypes were enriched for these 11 DMRs located in 13 genes (<i>EMILIN1</i>, <i>HOXA5</i>, <i>CPT1B</i>, <i>CLDN9</i>, <i>ZFP57</i>, <i>BRCA1</i>, <i>POU5F1</i>, <i>ANKRD33</i>, <i>HLA-B</i>, <i>RANBP17</i>, <i>ZMYND11</i>, <i>DIP2C</i>, <i>TMEM232</i>), highlighting the terms insulin resistance, and hyperglycaemia. Maternal DNAm was associated with foetal total thigh and arm tissues and subcutaneous thigh and arm fat, as well as with neonatal fat mass percentage and fat mass.</p><p><strong>Conclusion: </strong>The methylation pattern in the EGWG group indicated a risk for developing chronic diseases and involvement of maternal DNAm in foetal lean and fat mass and in neonatal fat mass.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057995","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":"Ribosomal Biogenesis and Heterogeneity in Development, Disease, and Aging.","authors":"Rowshan Ara Islam, Charalampos Rallis","doi":"10.3390/epigenomes7030017","DOIUrl":"10.3390/epigenomes7030017","url":null,"abstract":"<p><p>Although reported in the literature, ribosome heterogeneity is a phenomenon whose extent and implications in cell and organismal biology is not fully appreciated. This has been the case due to the lack of the appropriate techniques and approaches. Heterogeneity can arise from alternative use and differential content of protein and RNA constituents, as well as from post-transcriptional and post-translational modifications. In the few examples we have, it is apparent that ribosomal heterogeneity offers an additional level and potential for gene expression regulation and might be a way towards tuning metabolism, stress, and growth programs to external and internal stimuli and needs. Here, we introduce ribosome biogenesis and discuss ribosomal heterogeneity in various reported occasions. We conclude that a systematic approach in multiple organisms will be needed to delineate this biological phenomenon and its contributions to growth, aging, and disease. Finally, we discuss ribosome mutations and their roles in disease.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057997","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":"Evaluation of Exosomal miRNA as Potential Biomarkers in Cervical Cancer.","authors":"Jéssika Aline do Nascimento Medeiros,&nbsp;Ayane Cristine Alves Sarmento,&nbsp;Emanuelly Bernardes-Oliveira,&nbsp;Ronnier de Oliveira,&nbsp;Maysa Eunice Grigorio Bezerra Lima,&nbsp;Ana Katherine Gonçalves,&nbsp;Deyse de Souza Dantas,&nbsp;Janaina Cristiana de Oliveira Crispim","doi":"10.3390/epigenomes7030016","DOIUrl":"https://doi.org/10.3390/epigenomes7030016","url":null,"abstract":"<p><p>Different studies show that small non-coding RNAs, such as microRNAs (miRNAs) obtained from exosomes, are considered potential biomarkers in several types of cancer, including cervical cancer (CC). Therefore, the present study seeks to present an overview of the role of circulating exosomal miRNAs with the potential to act as biomarkers for the diagnosis and prognosis of CC and to analyze the presence of these miRNAs according to the stage of CC. For this purpose, a review was developed, with articles consulted from the electronic databases MEDLINE/PubMed, Scopus, and Web of Science published between 2015 and 2021. Seven articles were included after a selection of studies according to the eligibility criteria. In addition to the methods used for sample analysis, detection, and isolation of miRNAs in each article, clinical data were also extracted from the patients studied, such as the stage of cancer. After analyzing the network of the seven miRNAs, they were associated with the immune system, CC progression and staging, and cisplatin resistance. With the belief that studies on miRNAs in cervical cancer would have major clinical implications, in this review, we have attempted to summarize the current situation and potential development prospects.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10432889","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":"Association of Toll-Like Receptor Gene Polymorphisms with Tuberculosis in HIV-Positive Participants.","authors":"Svetlana Salamaikina,&nbsp;Vitaly Korchagin,&nbsp;Ekaterina Kulabukhova,&nbsp;Konstantin Mironov,&nbsp;Vera Zimina,&nbsp;Alexey Kravtchenko,&nbsp;Vasily Akimkin","doi":"10.3390/epigenomes7030015","DOIUrl":"https://doi.org/10.3390/epigenomes7030015","url":null,"abstract":"<p><p>Genetic factors in the HIV-background may play a significant role in the susceptibility to secondary diseases, like tuberculosis, which is the leading cause in mortality of HIV-positive people. Toll-like receptors (TLRs) are considered to be receptors for adaptive immunity, and polymorphisms in TLR genes can influence the activity of the immune response to infection. We conducted a case-control study of the association of TLR gene polymorphisms with the risk of tuberculosis coinfection in a multi-country sample of HIV-positive participants. Our study revealed certain associations between <i>TLR4</i> and <i>TLR6</i> polymorphisms and HIV-tuberculosis coinfection. We also found that the analyzed <i>TLR1</i> and <i>TLR4</i> polymorphisms were linked with the decline in CD4+ cell count, which is a predictor of disease progression in HIV-infected individuals. Our findings confirm that TLR gene polymorphisms are factors that may contribute to development of HIV-tuberculosis coinfection. However, the essence of the observed associations remains unclear, since it can also include both environmental factors and epigenetic mechanisms of gene expression regulation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10443360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048146","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":"Epigenetic Regulation in Heterosis and Environmental Stress: The Challenge of Producing Hybrid Epigenomes to Face Climate Change.","authors":"Fátima Duarte-Aké,&nbsp;Rosa Us-Camas,&nbsp;Clelia De-la-Peña","doi":"10.3390/epigenomes7030014","DOIUrl":"https://doi.org/10.3390/epigenomes7030014","url":null,"abstract":"<p><p>Epigenetic regulation has the potential to revolutionize plant breeding and improve crop yields by regulating gene expression in plants. DNA methylation and histone modifications are key epigenetic modifications that can impact plant development, stress responses, productivity, and yields. Higher-yielding crops not only generate greater profits for farmers and seed producers, but also require less land, water, fuel, and fertilizer than traditional crops for equivalent yields. The use of heterosis in crops can influence productivity and food quality, but producing hybrids with superior agronomic traits to their parents remains challenging. However, epigenetic markers, such as histone methylation and acetylation, may help select parental and hybrid combinations with better performances than the parental plants. This review assesses the potential applications of epigenetics in crop breeding and improvement, rendering agriculture more efficient, sustainable, and adaptable to changing environmental conditions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251564","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":"Pulmonary Pathogen-Induced Epigenetic Modifications.","authors":"Dylan Wrede, Mika Bordak, Yeabtsega Abraham, Masfique Mehedi","doi":"10.3390/epigenomes7030013","DOIUrl":"10.3390/epigenomes7030013","url":null,"abstract":"<p><p>Epigenetics generally involves genetic control by factors other than our own DNA sequence. Recent research has focused on delineating the mechanisms of two major epigenetic phenomena: DNA methylation and histone modification. As epigenetics involves many cellular processes, it is no surprise that it can also influence disease-associated gene expression. A direct link between respiratory infections, host cell epigenetic regulations, and chronic lung diseases is still unknown. Recent studies have revealed bacterium- or virus-induced epigenetic changes in the host cells. In this review, we focused on respiratory pathogens (viruses, bacteria, and fungi) induced epigenetic modulations (DNA methylation and histone modification) that may contribute to lung disease pathophysiology by promoting host defense or allowing pathogen persistence.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9874670","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":"Therapeutic Applications of Azanucleoside Analogs as DNA Demethylating Agents.","authors":"Fallon Gallimore,&nbsp;Tamer E Fandy","doi":"10.3390/epigenomes7030012","DOIUrl":"https://doi.org/10.3390/epigenomes7030012","url":null,"abstract":"<p><p>Azanucleosides, such as 5-azacytidine and decitabine, are DNA demethylating agents used in the treatment of acute myeloid leukemia and myelodysplastic syndromes. Researchers continue to explore their utility in the treatment of other hematologic and solid tumors. Based on the capacity of the compounds to inhibit DNA methyltransferase enzymes and the important role of DNA methylation in health and disease, it is essential to understand the molecular changes that azanucleosides induce and how these changes may improve treatment outcomes in subsets of patients. This review summarizes the molecular and therapeutic actions of azanucleosides and discusses recent clinical trials of these compounds as single agents or in combination therapy for the treatment of cancer and related conditions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10366911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10251566","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":"Graft-Derived Cell-Free DNA Quantification following Liver Transplantation Using Tissue-Specific DNA Methylation and Donor-Specific Genotyping Techniques: An Orthogonal Comparison Study.","authors":"Daniel R A Cox,&nbsp;Tess McClure,&nbsp;Fan Zhang,&nbsp;Boris Ka Leong Wong,&nbsp;Adam Testro,&nbsp;Su Kah Goh,&nbsp;Vijayaragavan Muralidharan,&nbsp;Alexander Dobrovic","doi":"10.3390/epigenomes7020011","DOIUrl":"https://doi.org/10.3390/epigenomes7020011","url":null,"abstract":"<p><p><i>Background</i>: Graft-derived cell-free DNA (gdcfDNA) analysis has shown promise as a non-invasive tool for monitoring organ health following solid organ transplantation. A number of gdcfDNA analysis techniques have been described; however, the majority rely on sequencing or prior genotyping to detect donor-recipient mis-matched genetic polymorphisms. Differentially methylated regions of DNA can be used to identify the tissue-of-origin of cell-free DNA (cfDNA) fragments. In this study, we aimed to directly compare the performance of gdcfDNA monitoring using graft-specific DNA methylation analysis and donor-recipient genotyping techniques in a pilot cohort of clinical samples from patients post-liver transplantation. <i>Results</i>: 7 patients were recruited prior to LT, 3 developed early, biopsy-proven TCMR in the first 6 weeks post-LT. gdcfDNA was successfully quantified in all samples using both approaches. There was a high level of technical correlation between results using the two techniques (Spearman testing, r_s = 0.87, <i>p</i> < 0.0001). gdcfDNA levels quantified using the genotyping approach were significantly greater across all timepoints in comparison to the tissue-specific DNA methylation-based approach: e.g., day 1 post-LT median 31,350 copies/mL (IQR 6731-64,058) vs. 4133 copies/mL (IQR 1100-8422), respectively. Qualitative trends in gdcfDNA levels for each patient were concordant between the two assays. Acute TCMR was preceded by significant elevations in gdcfDNA as quantified by both techniques. Elevations in gdcfDNA, using both techniques, were suggestive of TCMR in this pilot study with a 6- and 3-day lead-time prior to histological diagnosis in patients 1 and 2. <i>Conclusions</i>: Both the graft-specific methylation and genotyping techniques successfully quantified gdcfDNA in patients post-LT with statistically significant concordance. A direct comparison of these two techniques is not only important from a technical perspective for orthogonal validation, but significantly adds weight to the evidence that gdcfDNA monitoring reflects the underlying biology. Both techniques identified LT recipients who developed acute TCMR, with several days lead-time in comparison to conventional diagnostic workflows. Whilst the two assays performed comparably, gdcfDNA monitoring based on graft-specific DNA methylation patterns in cfDNA offers major practical advantages over the donor-recipient genotyping, and hence enhances the potential to translate this emerging technology into clinical practice.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10077635","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":"Histone Demethylase Modulation: Epigenetic Strategy to Combat Cancer Progression.","authors":"Rashmi Srivastava,&nbsp;Rubi Singh,&nbsp;Shaurya Jauhari,&nbsp;Niraj Lodhi,&nbsp;Rakesh Srivastava","doi":"10.3390/epigenomes7020010","DOIUrl":"https://doi.org/10.3390/epigenomes7020010","url":null,"abstract":"Epigenetic modifications are heritable, reversible changes in histones or the DNA that control gene functions, being exogenous to the genomic sequence itself. Human diseases, particularly cancer, are frequently connected to epigenetic dysregulations. One of them is histone methylation, which is a dynamically reversible and synchronously regulated process that orchestrates the three-dimensional epigenome, nuclear processes of transcription, DNA repair, cell cycle, and epigenetic functions, by adding or removing methylation groups to histones. Over the past few years, reversible histone methylation has become recognized as a crucial regulatory mechanism for the epigenome. With the development of numerous medications that target epigenetic regulators, epigenome-targeted therapy has been used in the treatment of malignancies and has shown meaningful therapeutic potential in preclinical and clinical trials. The present review focuses on the recent advances in our knowledge on the role of histone demethylases in tumor development and modulation, in emphasizing molecular mechanisms that control cancer cell progression. Finally, we emphasize current developments in the advent of new molecular inhibitors that target histone demethylases to regulate cancer progression.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9517956","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":"Critical Considerations for Investigating MicroRNAs during Tumorigenesis: A Case Study in Conceptual and Contextual Nuances of miR-211-5p in Melanoma.","authors":"Fatemeh Vand-Rajabpour, Meghan Savage, Rachel L Belote, Robert L Judson-Torres","doi":"10.3390/epigenomes7020009","DOIUrl":"10.3390/epigenomes7020009","url":null,"abstract":"<p><p>MicroRNAs are non-coding RNAs fundamental to metazoan development and disease. Although the aberrant regulation of microRNAs during mammalian tumorigenesis is well established, investigations into the contributions of individual microRNAs are wrought with conflicting observations. The underlying cause of these inconsistencies is often attributed to context-specific functions of microRNAs. We propose that consideration of both context-specific factors, as well as underappreciated fundamental concepts of microRNA biology, will permit a more harmonious interpretation of ostensibly diverging data. We discuss the theory that the biological function of microRNAs is to confer robustness to specific cell states. Through this lens, we then consider the role of miR-211-5p in melanoma progression. Using literature review and meta-analyses, we demonstrate how a deep understating of domain-specific contexts is critical for moving toward a concordant understanding of miR-211-5p and other microRNAs in cancer biology.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9772339","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}