Epigenomes最新文献

{"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":"Epigenetic Signatures of Centrosomes Are Novel Targets in Cancer Diagnosis: Insights from an Analysis of the Cancer Genome Atlas.","authors":"Zhou Zhang, Wei Zhang","doi":"10.3390/epigenomes6020014","DOIUrl":"10.3390/epigenomes6020014","url":null,"abstract":"<p><p>The centrosome plays a central role for cellular signaling and is critical for several fundamental cellular processes in human cells. Centrosome abnormalities have been linked to multiple solid tumors and hematological malignancies. We sought to explore the potential role of the DNA methylation, a critical epigenetic modification, of centrosome-related genes in different cancers. The 450K array DNA methylation data and RNA-seq data were downloaded for ~4000 tumor samples and ~500 normal controls from The Cancer Genome Atlas (TCGA) project, covering 11 major cancer types. Cancers with more than 30 normal controls were retained for analysis. Differentially modified CpGs of centrosome genes were identified, and cancer-specific epigenetic models were developed using a machine-learning algorithm for each cancer type. The association between the methylation level of differential CpGs and the corresponding gene expression, as well as the co-localization of the differential CpGs and cis-regulatory elements were evaluated. In total, 2761 CpGs located on 160 centrosome genes for 6 cancers were included in the analysis. Cancer-specific models demonstrated a high accuracy in terms of the area under the receiver operating characteristic (ROC) curve (AUC > 0.9) in five cancers and showed tissue specificity. This study enhanced our understanding of the epigenetic mechanisms underlying the DNA methylation of centrosome-related genes in cancers, and showed the potential of these epigenetic modifications as novel cancer biomarkers.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10868163","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":"The Transmission of Intergenerational Epigenetic Information by Sperm microRNAs.","authors":"Grace S Lee, Colin C Conine","doi":"10.3390/epigenomes6020012","DOIUrl":"10.3390/epigenomes6020012","url":null,"abstract":"<p><p>Epigenetic information is transmitted from one generation to the next, modulating the phenotype of offspring non-genetically in organisms ranging from plants to mammals. For intergenerational non-genetic inheritance to occur, epigenetic information must accumulate in germ cells. The three main carriers of epigenetic information-histone post-translational modifications, DNA modifications, and RNAs-all exhibit dynamic patterns of regulation during germ cell development. For example, histone modifications and DNA methylation are extensively reprogrammed and often eliminated during germ cell maturation and after fertilization during embryogenesis. Consequently, much attention has been given to RNAs, specifically small regulatory RNAs, as carriers of inherited epigenetic information. In this review, we discuss examples in which microRNAs have been implicated as key players in transmitting paternal epigenetic information intergenerationally.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10415183","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":"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}

{"title":"Opportunities for Early Cancer Detection: The Rise of ctDNA Methylation-Based Pan-Cancer Screening Technologies","authors":"Nicolas Constantin, A. A. I. Sina, D. Korbie, M. Trau","doi":"10.3390/epigenomes6010006","DOIUrl":"https://doi.org/10.3390/epigenomes6010006","url":null,"abstract":"The efficiency of conventional screening programs to identify early-stage malignancies can be limited by the low number of cancers recommended for screening as well as the high cumulative false-positive rate, and associated iatrogenic burden, resulting from repeated multimodal testing. The opportunity to use minimally invasive liquid biopsy testing to screen asymptomatic individuals at-risk for multiple cancers simultaneously could benefit from the aggregated diseases prevalence and a fixed specificity. Increasing both latter parameters is paramount to mediate high positive predictive value—a useful metric to evaluate a screening test accuracy and its potential harm-benefit. Thus, the use of a single test for multi-cancer early detection (stMCED) has emerged as an appealing strategy for increasing early cancer detection rate efficiency and benefit population health. A recent flurry of these stMCED technologies have been reported for clinical potential; however, their development is facing unique challenges to effectively improve clinical cost–benefit. One promising avenue is the analysis of circulating tumour DNA (ctDNA) for detecting DNA methylation biomarker fingerprints of malignancies—a hallmark of disease aetiology and progression holding the potential to be tissue- and cancer-type specific. Utilizing panels of epigenetic biomarkers could potentially help to detect earlier stages of malignancies as well as identify a tumour of origin from blood testing, useful information for follow-up clinical decision making and subsequent patient care improvement. Overall, this review collates the latest and most promising stMCED methodologies, summarizes their clinical performances, and discusses the specific requirements multi-cancer tests should meet to be successfully implemented into screening guidelines.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42590569","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}