Epigenomes最新文献

{"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}

{"title":"Acknowledgment to Reviewers of Epigenomes in 2021","authors":"","doi":"10.3390/epigenomes6010005","DOIUrl":"https://doi.org/10.3390/epigenomes6010005","url":null,"abstract":"Rigorous peer-reviews are the basis of high-quality academic publishing [...]","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42026313","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":"Biochemical Principles in Prion-Based Inheritance","authors":"Emily M. Dennis, David M. Garcia","doi":"10.3390/epigenomes6010004","DOIUrl":"https://doi.org/10.3390/epigenomes6010004","url":null,"abstract":"Prions are proteins that can stably fold into alternative structures that frequently alter their activities. They can self-template their alternate structures and are inherited across cell divisions and generations. While they have been studied for more than four decades, their enigmatic nature has limited their discovery. In the last decade, we have learned just how widespread they are in nature, the many beneficial phenotypes that they confer, while also learning more about their structures and modes of inheritance. Here, we provide a brief review of the biochemical principles of prion proteins, including their sequences, characteristics and structures, and what is known about how they self-template, citing examples from multiple organisms. Prion-based inheritance is the most understudied segment of epigenetics. Here, we lay a biochemical foundation and share a framework for how to define these molecules, as new examples are unearthed throughout nature.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44012824","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":"Polycomb Repressive Complex 2 in Eukaryotes-An Evolutionary Perspective.","authors":"Mallika Vijayanathan, María Guadalupe Trejo-Arellano, Iva Mozgová","doi":"10.3390/epigenomes6010003","DOIUrl":"10.3390/epigenomes6010003","url":null,"abstract":"<p><p>Polycomb repressive complex 2 (PRC2) represents a group of evolutionarily conserved multi-subunit complexes that repress gene transcription by introducing trimethylation of lysine 27 on histone 3 (H3K27me3). PRC2 activity is of key importance for cell identity specification and developmental phase transitions in animals and plants. The composition, biochemistry, and developmental function of PRC2 in animal and flowering plant model species are relatively well described. Recent evidence demonstrates the presence of PRC2 complexes in various eukaryotic supergroups, suggesting conservation of the complex and its function. Here, we provide an overview of the current understanding of PRC2-mediated repression in different representatives of eukaryotic supergroups with a focus on the green lineage. By comparison of PRC2 in different eukaryotes, we highlight the possible common and diverged features suggesting evolutionary implications and outline emerging questions and directions for future research of polycomb repression and its evolution.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39734184","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":"Chromatin Unlimited: An Evolutionary View of Chromatin.","authors":"Yasushi Hiraoka","doi":"10.3390/epigenomes6010002","DOIUrl":"https://doi.org/10.3390/epigenomes6010002","url":null,"abstract":"<p><p>Chromatin is a fundamental and highly conserved structure that carries genetic and epigenetic information in eukaryotic cells [...].</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39858491","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":"Epigenetics of Mitochondria-Associated Genes in Striated Muscle.","authors":"Kenneth C Ehrlich,&nbsp;Hong-Wen Deng,&nbsp;Melanie Ehrlich","doi":"10.3390/epigenomes6010001","DOIUrl":"https://doi.org/10.3390/epigenomes6010001","url":null,"abstract":"<p><p>Striated muscle has especially large energy demands. We identified 97 genes preferentially expressed in skeletal muscle and heart, but not in aorta, and found significant enrichment for mitochondrial associations among them. We compared the epigenomic and transcriptomic profiles of the 27 genes associated with striated muscle and mitochondria. Many showed strong correlations between their tissue-specific transcription levels, and their tissue-specific promoter, enhancer, or open chromatin as well as their DNA hypomethylation. Their striated muscle-specific enhancer chromatin was inside, upstream, or downstream of the gene, throughout much of the gene as a super-enhancer (<i>CKMT2</i>, <i>SLC25A4</i>, and <i>ACO2</i>), or even overlapping a neighboring gene (<i>COX6A2</i>, <i>COX7A1</i>, and <i>COQ10A</i>). Surprisingly, the 3' end of the 1.38 Mb <i>PRKN</i> (<i>PARK2</i>) gene (involved in mitophagy and linked to juvenile Parkinson's disease) displayed skeletal muscle/myoblast-specific enhancer chromatin, a myoblast-specific antisense RNA, as well as brain-specific enhancer chromatin. We also found novel tissue-specific RNAs in brain and embryonic stem cells within <i>PPARGC1A</i> (<i>PGC-1α</i>), which encodes a master transcriptional coregulator for mitochondrial formation and metabolism. The tissue specificity of this gene's four alternative promoters, including a muscle-associated promoter, correlated with nearby enhancer chromatin and open chromatin. Our in-depth epigenetic examination of these genes revealed previously undescribed tissue-specific enhancer chromatin, intragenic promoters, regions of DNA hypomethylation, and intragenic noncoding RNAs that give new insights into transcription control for this medically important set of genes.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2021-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8788487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264879","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":"Muscles in Winter: The Epigenetics of Metabolic Arrest.","authors":"W Aline Ingelson-Filpula,&nbsp;Kenneth B Storey","doi":"10.3390/epigenomes5040028","DOIUrl":"https://doi.org/10.3390/epigenomes5040028","url":null,"abstract":"<p><p>The winter months are challenging for many animal species, which often enter a state of dormancy or hypometabolism to \"wait out\" the cold weather, food scarcity, reduced daylight, and restricted mobility that can characterize the season. To survive, many species use metabolic rate depression (MRD) to suppress nonessential metabolic processes, conserving energy and limiting tissue atrophy particularly of skeletal and cardiac muscles. Mammalian hibernation is the best recognized example of winter MRD, but some turtle species spend the winter unable to breathe air and use MRD to survive with little or no oxygen (hypoxia/anoxia), and various frogs endure the freezing of about two-thirds of their total body water as extracellular ice. These winter survival strategies are highly effective, but create physiological and metabolic challenges that require specific biochemical adaptive strategies. Gene-related processes as well as epigenetic processes can lower the risk of atrophy during prolonged inactivity and limited nutrient stores, and DNA modifications, mRNA storage, and microRNA action are enacted to maintain and preserve muscle. This review article focuses on epigenetic controls on muscle metabolism that regulate MRD to avoid muscle atrophy and support winter survival in model species of hibernating mammals, anoxia-tolerant turtles and freeze-tolerant frogs. Such research may lead to human applications including muscle-wasting disorders such as sarcopenia, or other conditions of limited mobility.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"5 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2021-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39773350","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 Immune Remodeling of Mesothelioma Cells: A New Strategy to Improve the Efficacy of Immunotherapy.","authors":"Maria Fortunata Lofiego,&nbsp;Sara Cannito,&nbsp;Carolina Fazio,&nbsp;Francesca Piazzini,&nbsp;Ornella Cutaia,&nbsp;Laura Solmonese,&nbsp;Francesco Marzani,&nbsp;Carla Chiarucci,&nbsp;Anna Maria Di Giacomo,&nbsp;Luana Calabrò,&nbsp;Sandra Coral,&nbsp;Michele Maio,&nbsp;Alessia Covre,&nbsp;On Behalf Of The EPigenetic Immune-Oncology Consortium Airc Epica Investigators","doi":"10.3390/epigenomes5040027","DOIUrl":"https://doi.org/10.3390/epigenomes5040027","url":null,"abstract":"<p><p>Malignant pleural mesothelioma (MPM) is an aggressive malignancy with a severe prognosis, and with a long-standing need for more effective therapeutic approaches. However, treatment with immune checkpoint inhibitors is becoming an increasingly effective strategy for MPM patients. In this scenario, epigenetic modifications may negatively regulate the interplay between immune and malignant cells within the tumor microenvironment, thus contributing to the highly immunosuppressive contexture of MPM that may limit the efficacy of immunotherapy. Aiming to further improve prospectively the clinical efficacy of immunotherapeutic approaches in MPM, we investigated the immunomodulatory potential of different classes of epigenetic drugs (i.e., DNA hypomethylating agent (DHA) guadecitabine, histone deacetylase inhibitors VPA and SAHA, or EZH2 inhibitors EPZ-6438) in epithelioid, biphasic, and sarcomatoid MPM cell lines, by cytofluorimetric and real-time PCR analyses. We also characterized the effects of the DHA, guadecitabine, on the gene expression profiles (GEP) of the investigated MPM cell lines by the nCounter platform. Among investigated drugs, exposure of MPM cells to guadecitabine, either alone or in combination with VPA, SAHA and EPZ-6438 demonstrated to be the main driver of the induction/upregulation of immune molecules functionally crucial in host-tumor interaction (i.e., HLA class I, ICAM-1 and cancer testis antigens) in all three MPM subtypes investigated. Additionally, GEP demonstrated that treatment with guadecitabine led to the activation of genes involved in several immune-related functional classes mainly in the sarcomatoid subtype. Furthermore, among investigated MPM subtypes, DHA-induced CDH1 expression that contributes to restoring the epithelial phenotype was highest in sarcomatoid cells. Altogether, our results contribute to providing the rationale to develop new epigenetically-based immunotherapeutic approaches for MPM patients, potentially tailored to the specific histologic subtypes.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"5 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2021-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8715476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39772999","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":"G9a: An Emerging Epigenetic Target for Melanoma Therapy.","authors":"Jessica L Flesher,&nbsp;David E Fisher","doi":"10.3390/epigenomes5040023","DOIUrl":"https://doi.org/10.3390/epigenomes5040023","url":null,"abstract":"<p><p>Epigenetic regulation is a crucial component of DNA maintenance and cellular identity. As our understanding of the vast array of proteins that contribute to chromatin accessibility has advanced, the role of epigenetic remodelers in disease has become more apparent. G9a is a histone methyltransferase that contributes to immune cell differentiation and function, neuronal development, and has been implicated in diseases, including cancer. In melanoma, recurrent mutations and amplifications of G9a have led to its identification as a therapeutic target. The pathways that are regulated by G9a provide an insight into relevant biomarkers for patient stratification. Future work is aided by the breadth of literature on G9a function during normal differentiation and development, along with similarities to EZH2, another histone methyltransferase that forms a synthetic lethal relationship with members of the SWI/SNF complex in certain cancers. Here, we review the literature on G9a, its role in melanoma, and lessons from EZH2 inhibitor studies.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"5 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8536146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39555677","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}