Epigenomes最新文献

{"title":"Experimental and Computational Approaches for Non-CpG Methylation Analysis.","authors":"Deepa Ramasamy,&nbsp;Arunagiri Kuha Deva Magendhra Rao,&nbsp;Thangarajan Rajkumar,&nbsp;Samson Mani","doi":"10.3390/epigenomes6030024","DOIUrl":"https://doi.org/10.3390/epigenomes6030024","url":null,"abstract":"<p><p>Cytosine methylation adjacent to adenine, thymine, and cytosine residues but not guanine of the DNA is distinctively known as non-CpG methylation. This CA/CT/CC methylation accounts for 15% of the total cytosine methylation and varies among different cell and tissue types. The abundance of CpG methylation has largely concealed the role of non-CpG methylation. Limitations in the early detection methods could not distinguish CpG methylation from non-CpG methylation. Recent advancements in enrichment strategies and high throughput sequencing technologies have enabled the detection of non-CpG methylation. This review discusses the advanced experimental and computational approaches to detect and describe the genomic distribution and function of non-CpG methylation. We present different approaches such as enzyme-based and antibody-based enrichment, which, when coupled, can also improve the sensitivity and specificity of non-CpG detection. We also describe the current bioinformatics pipelines and their specific application in computing and visualizing the imbalance of CpG and non-CpG methylation. Enrichment modes and the computational suites need to be further developed to ease the challenges of understanding the functional role of non-CpG methylation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649120","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 Role of Polycomb Proteins in Cell Lineage Commitment and Embryonic Development.","authors":"Chet H Loh,&nbsp;Gert Jan C Veenstra","doi":"10.3390/epigenomes6030023","DOIUrl":"https://doi.org/10.3390/epigenomes6030023","url":null,"abstract":"<p><p>Embryonic development is a highly intricate and complex process. Different regulatory mechanisms cooperatively dictate the fate of cells as they progress from pluripotent stem cells to terminally differentiated cell types in tissues. A crucial regulator of these processes is the Polycomb Repressive Complex 2 (PRC2). By catalyzing the mono-, di-, and tri-methylation of lysine residues on histone H3 tails (H3K27me3), PRC2 compacts chromatin by cooperating with Polycomb Repressive Complex 1 (PRC1) and represses transcription of target genes. Proteomic and biochemical studies have revealed two variant complexes of PRC2, namely PRC2.1 which consists of the core proteins (EZH2, SUZ12, EED, and RBBP4/7) interacting with one of the Polycomb-like proteins (MTF2, PHF1, PHF19), and EPOP or PALI1/2, and PRC2.2 which contains JARID2 and AEBP2 proteins. MTF2 and JARID2 have been discovered to have crucial roles in directing and recruiting PRC2 to target genes for repression in embryonic stem cells (ESCs). Following these findings, recent work in the field has begun to explore the roles of different PRC2 variant complexes during different stages of embryonic development, by examining molecular phenotypes of PRC2 mutants in both in vitro (2D and 3D differentiation) and in vivo (knock-out mice) assays, analyzed with modern single-cell omics and biochemical assays. In this review, we discuss the latest findings that uncovered the roles of different PRC2 proteins during cell-fate and lineage specification and extrapolate these findings to define a developmental roadmap for different flavors of PRC2 regulation during mammalian embryonic development.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40649119","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":"Clinical Epigenetics on the Baltic Coast.","authors":"Ryszard Maleszka","doi":"10.3390/epigenomes6030019","DOIUrl":"https://doi.org/10.3390/epigenomes6030019","url":null,"abstract":"<p><p>This report summarizes the proceedings of the inaugural Clinical Epigenetics Conference that was held in Szczecin, Poland, from 8 June 2022. With focus on epigenetic diseases whose causes, progression, and prognosis are associated with aberrant epigenomic alterations, the meeting was a timely forum to discuss recent progress in this rapidly evolving field and consider avenues for converting experimental data into clinical reality that would be beneficial for patients. The wealth of the presented data was an impressive showcase of the enormous challenges faced by researchers in their quest for understanding the benefits and limitations of the available information in the medical context. A shared view among the participants was that merging the current state of knowledge with clinical applications will be promptly achieved.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647022","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":"Epidrugs: Toward Understanding and Treating Diverse Diseases.","authors":"Takashi Umehara","doi":"10.3390/epigenomes6030018","DOIUrl":"https://doi.org/10.3390/epigenomes6030018","url":null,"abstract":"<p><p>Epigenomic modifications are unique in the type and amount of chemical modification at each chromosomal location, can vary from cell to cell, and can be externally modulated by small molecules. In recent years, genome-wide epigenomic modifications have been revealed, and rapid progress has been made in the identification of proteins responsible for epigenomic modifications and in the development of compounds that regulate them. This Special Issue on \"Epidrugs: Toward Understanding and Treating Diverse Diseases\" aims to provide insights into various aspects of the biology and development of epigenome-regulating compounds.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647021","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 m6A RNA Methylation in SARS-CoV-2 Positive Nasopharyngeal Samples in a Mexican Population: A First Approximation Study.","authors":"Jorge Luis Batista-Roche,&nbsp;Bruno Gómez-Gil,&nbsp;Gertrud Lund,&nbsp;César Alejandro Berlanga-Robles,&nbsp;Alejandra García-Gasca","doi":"10.3390/epigenomes6030016","DOIUrl":"https://doi.org/10.3390/epigenomes6030016","url":null,"abstract":"<p><p>The Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the causal agent of COVID-19 (Coronavirus Disease-19). Both mutation and/or recombination events in the SARS-CoV-2 genome have resulted in variants that differ in transmissibility and severity. Furthermore, RNA methylation of the N6 position of adenosine (m6A) is known to be altered in cells infected with SARS-CoV-2. However, it is not known whether this epitranscriptomic modification differs across individuals dependent on the presence of infection with distinct SARS-CoV-2 variants, the viral load, or the vaccination status. To address this issue, we selected RNAs (<i>n</i> = 60) from SARS-CoV-2 sequenced nasopharyngeal samples (<i>n</i> = 404) of 30- to 60-year-old outpatients or hospitalized individuals from the city of Mazatlán (Mexico) between February 2021 and March 2022. Control samples were non-infected individuals (<i>n</i> = 10). SARS-CoV-2 was determined with real-time PCR, viral variants were determined with sequencing, and global m6A levels were determined by using a competitive immunoassay method. We identified variants of concern (VOC; alpha, gamma, delta, omicron), the variant of interest (VOI; epsilon), and the lineage B.1.1.519. Global m6A methylation differed significantly across viral variants (<i>p</i> = 3.2 × 10^-7). In particular, we found that m6A levels were significantly lower in the VOC delta- and omicron-positive individuals compared to non-infected individuals (<i>p</i> = 2.541236 × 10^-2 and 1.134411 × 10^-4, respectively). However, we uncovered no significant correlation between global m6A levels and viral nucleocapsid (<i>N</i>) gene expression or age. Furthermore, individuals with complete vaccination schemes showed significantly lower m6A levels than unvaccinated individuals (<i>p</i> = 2.6 × 10^-4), and differences in methylation levels across variants in unvaccinated individuals were significant (<i>p</i> = 3.068 × 10^-3). These preliminary results suggest that SARS-CoV-2 variants show differences in global m6A levels.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40647020","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":"Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19","authors":"S. Sarkar, Rwik Sen","doi":"10.3390/epigenomes6020013","DOIUrl":"https://doi.org/10.3390/epigenomes6020013","url":null,"abstract":"Although few in number, studies on epigenome of the heart of COVID-19 patients show that epigenetic signatures such as DNA methylation are significantly altered, leading to changes in expression of several genes. It contributes to pathogenic cardiac phenotypes of COVID-19, e.g., low heart rate, myocardial edema, and myofibrillar disarray. DNA methylation studies reveal changes which likely contribute to cardiac disease through unknown mechanisms. The incidence of severe COVID-19 disease, including hospitalization, requiring respiratory support, morbidity, and mortality, is disproportionately higher in individuals with co-morbidities. This poses unprecedented strains on the global healthcare system. While their underlying conditions make patients more susceptible to severe COVID-19 disease, strained healthcare systems, lack of adequate support, or sedentary lifestyles from ongoing lockdowns have proved detrimental to their underlying health conditions, thus pushing them to severe risk of congenital heart disease (CHD) itself. Prophylactic vaccines against COVID-19 have ushered new hope for CHD. A common connection between COVID-19 and CHD is SARS-CoV-2’s host receptor ACE2, because ACE2 regulates and protects organs, including the heart, in various ways. ACE2 is a common therapeutic target against cardiovascular disease and COVID-19 which damages organs. Hence, this review explores the above regarding CHDs, cardiovascular damage, and cardiac epigenetics, in COVID-19 patients.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46205557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Expression of Non-Coding RNA Fragments in Frontal Cortex, Hippocampus and Cerebellum of Rats","authors":"Anna Fiselier, Boseon Byeon, Y. Ilnytskyy, I. Kovalchuk, O. Kovalchuk","doi":"10.3390/epigenomes6020011","DOIUrl":"https://doi.org/10.3390/epigenomes6020011","url":null,"abstract":"Non-coding RNA fragments (ncRFs) are processed from various non-coding RNAs (ncRNAs), with the most abundant being those produced from tRNAs. ncRFs were reported in many animal and plant species. Many ncRFs exhibit tissue specificity or/and are affected by stress. There is, however, only a handful of reports that describe differential expression of ncRFs in the brain regions. In this work, we analyzed the abundance of ncRFs processed from four major ncRNAs, including tRNA (tRFs), snoRNA (snoRFs), snRNA (snRFs), and rRNA (rRFs) in the frontal cortex (FC), hippocampus (HIP), and cerebellum (CER) of male and female rats. We found brain-specific and sex-specific differences. Reads mapping to lincRNAs were significantly larger in CER as compared to HIP and CER, while those mapping to snRNAs and tRNA were smaller in HIP than in FC and CER. tRF reads were the most abundant among all ncRF reads, and FC had more reads than HIP and CER. Reads mapping to antisense ncRNAs were significantly larger in females than in males in FC. Additionally, males consistently had more tRF, snRF, and snoRF reads in all brain regions. rRFs were more abundant in males in FC and females in HIP. Several tRFs were significantly underrepresented, including tRF-ValCAC, tRF-ValACC, and tRF-LysCTT in all brain regions. We also found brain- and sex-specific differences in the number of brain function-related mRNA targets. To summarize, we found sex-specific differences in the expression of several ncRNA fragments in various brain regions of healthy rats.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42833492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SWI/SNF Chromatin Remodeling Enzymes in Melanoma.","authors":"Megan R Dreier,&nbsp;Ivana L de la Serna","doi":"10.3390/epigenomes6010010","DOIUrl":"https://doi.org/10.3390/epigenomes6010010","url":null,"abstract":"<p><p>Melanoma is an aggressive malignancy that arises from the transformation of melanocytes on the skin, mucosal membranes, and uvea of the eye. SWI/SNF chromatin remodeling enzymes are multi-subunit complexes that play important roles in the development of the melanocyte lineage and in the response to ultraviolet radiation, a key environmental risk factor for developing cutaneous melanoma. Exome sequencing has revealed frequent loss of function mutations in genes encoding SWI/SNF subunits in melanoma. However, some SWI/SNF subunits have also been demonstrated to have pro-tumorigenic roles in melanoma and to affect sensitivity to therapeutics. This review summarizes studies that have implicated SWI/SNF components in melanomagenesis and have evaluated how SWI/SNF subunits modulate the response to current therapeutics.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8947417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318107","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 Importance of Networking: Plant Polycomb Repressive Complex 2 and Its Interactors.","authors":"James Godwin,&nbsp;Sara Farrona","doi":"10.3390/epigenomes6010008","DOIUrl":"https://doi.org/10.3390/epigenomes6010008","url":null,"abstract":"<p><p>Polycomb Repressive Complex 2 (PRC2) is arguably the best-known plant complex of the Polycomb Group (PcG) pathway, formed by a group of proteins that epigenetically represses gene expression. PRC2-mediated deposition of H3K27me3 has amply been studied in Arabidopsis and, more recently, data from other plant model species has also been published, allowing for an increasing knowledge of PRC2 activities and target genes. How PRC2 molecular functions are regulated and how PRC2 is recruited to discrete chromatin regions are questions that have brought more attention in recent years. A mechanism to modulate PRC2-mediated activity is through its interaction with other protein partners or accessory proteins. Current evidence for PRC2 interactors has demonstrated the complexity of its protein network and how far we are from fully understanding the impact of these interactions on the activities of PRC2 core subunits and on the formation of new PRC2 versions. This review presents a list of PRC2 interactors, emphasizing their mechanistic action upon PRC2 functions and their effects on transcriptional regulation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40318105","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":"Methylation Status of Exon IV of the Brain-Derived Neurotrophic Factor (BDNF)-Encoding Gene in Patients with Non-Diabetic Hyperglycaemia (NDH) before and after a Lifestyle Intervention","authors":"H. Fachim, N. Malipatil, K. Siddals, R. Donn, Gabriela Y. Cortés, C. Dalton, J. Gibson, A. Heald","doi":"10.3390/epigenomes6010007","DOIUrl":"https://doi.org/10.3390/epigenomes6010007","url":null,"abstract":"BDNF signalling in hypothalamic neuronal circuits is thought to regulate mammalian food intake. In light of this, we investigated how a lifestyle intervention influenced serum levels and DNA methylation of BDNF gene in fat tissue and buffy coat of NDH individuals. In total, 20 participants underwent anthropometric measurements/fasting blood tests and adipose tissue biopsy pre-/post-lifestyle (6 months) intervention. DNA was extracted from adipose tissue and buffy coat, bisulphite converted, and pyrosequencing was used to determine methylation levels in exon IV of the BDNF gene. RNA was extracted from buffy coat for gene expression analysis and serum BDNF levels were measured by ELISA. No differences were found in BDNF serum levels, but buffy coat mean BDNF gene methylation decreased post-intervention. There were correlations between BDNF serum levels and/or methylation and cardiometabolic markers. (i) Pre-intervention: for BDNF methylation, we found positive correlations between mean methylation in fat tissue and waist-hip ratio, and negative correlations between mean methylation in buffy coat and weight. (ii) Post-intervention: we found correlations between BDNF mean methylation in buffy coat and HbA1c, BDNF methylation in buffy coat and circulating IGFBP-2, and BDNF serum and insulin. Higher BDNF % methylation levels are known to reduce BNDF expression. The fall in buffy coat mean BDNF methylation plus the association between lower BDNF methylation (so potentially higher BDNF) and higher HbA1c and serum IGFBP-2 (as a marker of insulin sensitivity) and between lower serum BDNF and higher circulating insulin are evidence for the degree of BDNF gene methylation being implicated in insulinisation and glucose homeostasis, particularly after lifestyle change in NDH individuals.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69823677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}