Epigenomes最新文献

{"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}

{"title":"Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress.","authors":"Mariya A Smetanina,&nbsp;Valeria A Korolenya,&nbsp;Alexander E Kel,&nbsp;Ksenia S Sevostyanova,&nbsp;Konstantin A Gavrilov,&nbsp;Andrey I Shevela,&nbsp;Maxim L Filipenko","doi":"10.3390/epigenomes7010008","DOIUrl":"https://doi.org/10.3390/epigenomes7010008","url":null,"abstract":"<p><p>Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory shear stress or left at the static condition. Then, other cell types were treated with preconditioned media from the adjacent layer's cells. DNA isolated from the harvested cells was subjected to epigenome-wide study using Illumina microarrays followed by data analysis with GenomeStudio (Illumina), Excel (Microsoft), and Genome Enhancer (geneXplain) software packages. Differential (hypo-/hyper-) methylation was revealed for each cell layer's DNA. The most targetable master regulators controlling the activity of certain transcription factors regulating the genes near the differentially methylated sites appeared to be the following: (1) HGS, PDGFB, and AR for endothelial cells; (2) HGS, CDH2, SPRY2, SMAD2, ZFYVE9, and P2RY1 for smooth muscle cells; and (3) WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN for fibroblasts. Some of the identified master regulators may serve as promising druggable targets for treating varicose veins in the future.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9204662","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":"Chemical Inhibitors Targeting the Histone Lysine Demethylase Families with Potential for Drug Discovery.","authors":"Nando Dulal Das,&nbsp;Hideaki Niwa,&nbsp;Takashi Umehara","doi":"10.3390/epigenomes7010007","DOIUrl":"https://doi.org/10.3390/epigenomes7010007","url":null,"abstract":"<p><p>The dynamic regulation of histone methylation and demethylation plays an important role in the regulation of gene expression. Aberrant expression of histone lysine demethylases has been implicated in various diseases including intractable cancers, and thus lysine demethylases serve as promising therapeutic targets. Recent studies in epigenomics and chemical biology have led to the development of a series of small-molecule demethylase inhibitors that are potent, specific, and have in vivo efficacy. In this review, we highlight emerging small-molecule inhibitors targeting the histone lysine demethylases and their progress toward drug discovery.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9204661","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 Breast Cancer: Insights on Epidrugs.","authors":"Ayoung Kim,&nbsp;Kyumin Mo,&nbsp;Hyeonseok Kwon,&nbsp;Soohyun Choe,&nbsp;Misung Park,&nbsp;Woori Kwak,&nbsp;Hyunho Yoon","doi":"10.3390/epigenomes7010006","DOIUrl":"https://doi.org/10.3390/epigenomes7010006","url":null,"abstract":"<p><p>Breast cancer remains a common cause of cancer-related death in women. Therefore, further studies are necessary for the comprehension of breast cancer and the revolution of breast cancer treatment. Cancer is a heterogeneous disease that results from epigenetic alterations in normal cells. Aberrant epigenetic regulation is strongly associated with the development of breast cancer. Current therapeutic approaches target epigenetic alterations rather than genetic mutations due to their reversibility. The formation and maintenance of epigenetic changes depend on specific enzymes, including DNA methyltransferases and histone deacetylases, which are promising targets for epigenetic-based therapy. Epidrugs target different epigenetic alterations, including DNA methylation, histone acetylation, and histone methylation, which can restore normal cellular memory in cancerous diseases. Epigenetic-targeted therapy using epidrugs has anti-tumor effects on malignancies, including breast cancer. This review focuses on the importance of epigenetic regulation and the clinical implications of epidrugs in breast cancer.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10786447","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":"<i>SNCA</i> Gene Methylation in Parkinson's Disease and Multiple System Atrophy.","authors":"Ekaterina Yu Fedotova,&nbsp;Elena V Iakovenko,&nbsp;Natalia Yu Abramycheva,&nbsp;Sergey N Illarioshkin","doi":"10.3390/epigenomes7010005","DOIUrl":"https://doi.org/10.3390/epigenomes7010005","url":null,"abstract":"<p><p>In recent years, epigenetic mechanisms have been implicated in the development of multifactorial diseases including neurodegenerative disorders. In Parkinson's disease (PD), as a synucleinopathy, most studies focused on DNA methylation of <i>SNCA</i> gene coding alpha-synuclein but obtained results were rather contradictory. In another neurodegenerative synucleinopathy, multiple system atrophy (MSA), very few studies investigated the epigenetic regulation. This study included patients with PD (n = 82), patients with MSA (n = 24), and a control group (n = 50). In three groups, methylation levels of CpG and non-CpG sites in regulatory regions of the <i>SNCA</i> gene were analyzed. We revealed hypomethylation of CpG sites in the <i>SNCA</i> intron 1 in PD and hypermethylation of predominantly non-CpG sites in the <i>SNCA</i> promoter region in MSA. In PD patients, hypomethylation in the intron 1 was associated with earlier age at the disease onset. In MSA patients, hypermethylation in the promotor was associated with shorter disease duration (before examination). These results showed different patterns of the epigenetic regulation in two synucleinopathies-PD and MSA.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9313046","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":"DNA Methylation Is a Potential Biomarker for Cardiometabolic Health in Mexican Children and Adolescents.","authors":"Abeer A Aljahdali, Jaclyn M Goodrich, Dana C Dolinoy, Hyungjin M Kim, Edward A Ruiz-Narváez, Ana Baylin, Alejandra Cantoral, Libni A Torres-Olascoaga, Martha M Téllez-Rojo, Karen E Peterson","doi":"10.3390/epigenomes7010004","DOIUrl":"10.3390/epigenomes7010004","url":null,"abstract":"<p><p>DNA methylation (DNAm) is a plausible mechanism underlying cardiometabolic abnormalities, but evidence is limited among youth. This analysis included 410 offspring of the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohort followed up to two time points in late childhood/adolescence. At Time 1, DNAm was quantified in blood leukocytes at long interspersed nuclear elements (LINE-1), <i>H19</i>, and 11β-hydroxysteroid dehydrogenase type 2 (<i>11β-HSD-2</i>), and at Time 2 in peroxisome proliferator-activated receptor alpha (<i>PPAR-α</i>). At each time point, cardiometabolic risk factors were assessed including lipid profiles, glucose, blood pressure, and anthropometry. Linear mixed effects models were used for LINE-1, <i>H19</i>, and <i>11β-HSD-2</i> to account for the repeated-measure outcomes. Linear regression models were conducted for the cross-sectional association between <i>PPAR-α</i> with the outcomes. DNAm at LINE-1 was associated with log glucose at site 1 [β = -0.029, <i>p</i> = 0.0006] and with log high-density lipoprotein cholesterol at site 3 [β = 0.063, <i>p</i> = 0.0072]. <i>11β-HSD-2</i> DNAm at site 4 was associated with log glucose (β = -0.018, <i>p</i> = 0.0018). DNAm at LINE-1 and <i>11β-HSD-2</i> was associated with few cardiometabolic risk factors among youth in a locus-specific manner. These findings underscore the potential for epigenetic biomarkers to increase our understanding of cardiometabolic risk earlier in life.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9581475","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}