Epigenomes最新文献

{"title":"Epigenetic Regulation of Mammalian Cardiomyocyte Development.","authors":"Isaiah K Mensah, Humaira Gowher","doi":"10.3390/epigenomes8030025","DOIUrl":"10.3390/epigenomes8030025","url":null,"abstract":"<p><p>The heart is the first organ formed during mammalian development and functions to distribute nutrients and oxygen to other parts of the developing embryo. Cardiomyocytes are the major cell types of the heart and provide both structural support and contractile function to the heart. The successful differentiation of cardiomyocytes during early development is under tight regulation by physical and molecular factors. We have reviewed current studies on epigenetic factors critical for cardiomyocyte differentiation, including DNA methylation, histone modifications, chromatin remodelers, and noncoding RNAs. This review also provides comprehensive details on structural and morphological changes associated with the differentiation of fetal and postnatal cardiomyocytes and highlights their differences. A holistic understanding of all aspects of cardiomyocyte development is critical for the successful in vitro differentiation of cardiomyocytes for therapeutic purposes.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270418/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762943","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 Hypomethylation Underlies Epigenetic Swapping between <i>AGO1</i> and <i>AGO1-V2</i> Isoforms in Tumors.","authors":"Jean S Fain, Camille Wangermez, Axelle Loriot, Claudia Denoue, Charles De Smet","doi":"10.3390/epigenomes8030024","DOIUrl":"10.3390/epigenomes8030024","url":null,"abstract":"<p><p>Human tumors progress in part by accumulating epigenetic alterations, which include gains and losses of DNA methylation in different parts of the cancer cell genome. Recent work has revealed a link between these two opposite alterations by showing that DNA hypomethylation in tumors can induce the expression of transcripts that overlap downstream gene promoters and thereby induce their hypermethylation. Preliminary in silico evidence prompted us to investigate if this mechanism applies to the locus harboring <i>AGO1</i>, a gene that plays a central role in miRNA biogenesis and RNA interference. Inspection of public RNA-Seq datasets and RT-qPCR experiments show that an alternative transcript starting 13.4 kb upstream of <i>AGO1</i> (<i>AGO1-V2</i>) is expressed specifically in testicular germ cells, and becomes aberrantly activated in different types of tumors, particularly in tumors of the esophagus, stomach, and lung. This expression pattern classifies <i>AGO1-V2</i> into the group of \"Cancer-Germline\" (CG) genes. Analysis of transcriptomic and methylomic datasets provided evidence that transcriptional activation of <i>AGO1-V2</i> depends on DNA demethylation of its promoter region. Western blot experiments revealed that <i>AGO1-V2</i> encodes a shortened isoform of AGO1, corresponding to a truncation of 75 aa in the N-terminal domain, and which we therefore referred to as \"∆NAGO1\". Interestingly, significant correlations between hypomethylation/activation of <i>AGO1-V2</i> and hypermethylation/repression of <i>AGO1</i> were observed upon examination of tumor cell lines and tissue datasets. Overall, our study reveals the existence of a process of interdependent epigenetic alterations in the <i>AGO1</i> locus, which promotes swapping between two AGO1 protein-coding mRNA isoforms in tumors.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11270204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762942","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":"Keep Fingers on the CpG Islands.","authors":"Xing Zhang, Robert M Blumenthal, Xiaodong Cheng","doi":"10.3390/epigenomes8020023","DOIUrl":"10.3390/epigenomes8020023","url":null,"abstract":"<p><p>The post-genomic era has ushered in the extensive application of epigenetic editing tools, allowing for precise alterations of gene expression. The use of reprogrammable editors that carry transcriptional corepressors has significant potential for long-term epigenetic silencing for the treatment of human diseases. The ideal scenario involves precise targeting of a specific genomic location by a DNA-binding domain, ensuring there are no off-target effects and that the process yields no genetic remnants aside from specific epigenetic modifications (i.e., DNA methylation). A notable example is a recent study on the mouse <i>Pcsk9</i> gene, crucial for cholesterol regulation and expressed in hepatocytes, which identified synthetic zinc-finger (ZF) proteins as the most effective DNA-binding editors for silencing <i>Pcsk9</i> efficiently, specifically, and persistently. This discussion focuses on enhancing the specificity of ZF-array DNA binding by optimizing interactions between specific amino acids and DNA bases across three promoters containing CpG islands.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11202855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452293","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":"Structural and Biochemical Characterization of the Nucleosome Containing Variants H3.3 and H2A.Z.","authors":"Harry Jung, Vladyslava Sokolova, Gahyun Lee, Victoria Rose Stevens, Dongyan Tan","doi":"10.3390/epigenomes8020021","DOIUrl":"10.3390/epigenomes8020021","url":null,"abstract":"<p><p>Variant H3.3, along with H2A.Z, is notably enriched at promoter regions and is commonly associated with transcriptional activation. However, the specific molecular mechanisms through which H3.3 influences chromatin dynamics at transcription start sites, and its role in gene regulation, remain elusive. Using a combination of biochemistry and cryo-electron microscopy (cryo-EM), we show that the inclusion of H3.3 alone does not induce discernible changes in nucleosome DNA dynamics. Conversely, the presence of both H3.3 and H2A.Z enhances DNA's flexibility similarly to H2A.Z alone. Interestingly, our findings suggest that the presence of H3.3 in the H2A.Z nucleosome provides slightly increased protection to DNA at internal sites within the nucleosome. These results imply that while H2A.Z at active promoters promotes the formation of more accessible nucleosomes with increased DNA accessibility to facilitate transcription, the simultaneous presence of H3.3 offers an additional mechanism to fine-tune nucleosome accessibility and the chromatin environment.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11203148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452294","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":"Blood Vitamin C Levels of Patients Receiving Immunotherapy and Relationship to Monocyte Subtype and Epigenetic Modification.","authors":"Ben Topham, Millie de Vries, Maria Nonis, Rebecca van Berkel, Juliet M Pullar, Nicholas J Magon, Margreet C M Vissers, Margaret J Currie, Bridget A Robinson, David Gibbs, Abel Ang, Gabi U Dachs","doi":"10.3390/epigenomes8020017","DOIUrl":"10.3390/epigenomes8020017","url":null,"abstract":"<p><p>The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158953","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":"Deciphering the Diversity in Bacterial Transporters That Salvage Queuosine Precursors.","authors":"Samia Quaiyum, Yifeng Yuan, Paul J Kuipers, Maria Martinelli, Marshall Jaroch, Valérie de Crécy-Lagard","doi":"10.3390/epigenomes8020016","DOIUrl":"10.3390/epigenomes8020016","url":null,"abstract":"<p><p>Queuosine (Q) is a modification of the wobble base of tRNA harboring GUN anticodons with roles in decoding accuracy and efficiency. Its synthesis is complex with multiple enzymatic steps, and several pathway intermediates can be salvaged. The only two transporter families known to salvage Q precursors are QPTR/COG1738 and QrtT/QueT. Analyses of the distribution of known Q synthesis and salvage genes in human gut and oral microbiota genomes have suggested that more transporter families remain to be found and that Q precursor exchanges must occur within the structured microenvironments of the mammalian host. Using physical clustering and fusion-based association with Q salvage genes, candidate genes for missing transporters were identified and five were tested experimentally by complementation assays in <i>Escherichia coli</i>. Three genes encoding transporters from three different Pfam families, a ureide permease (PF07168) from <i>Acidobacteriota</i> bacterium, a hemolysin III family protein (PF03006) from <i>Bifidobacterium breve</i>, and a Major Facilitator Superfamily protein (PF07690) from <i>Bartonella henselae</i>, were found to allow the transport of both preQ₀ and preQ₁ in this heterologous system. This work suggests that many transporter families can evolve to transport Q precursors, reinforcing the concept of transporter plasticity.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158955","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 Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during Adolescence.","authors":"Mohammad Nahian Ferdous Abrar, Yu Jiang, Hongmei Zhang, Liang Li, Hasan Arshad","doi":"10.3390/epigenomes8020012","DOIUrl":"10.3390/epigenomes8020012","url":null,"abstract":"<p><p>The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) has been shown to be associated with asthma risk and its severity. However, the role of LF in the associations between DNAm and AA is unclear, and it is also unknown whether the association between DNAm and AA is consistent with that between DNAm and LF. We address this question through assessing newborn epigenetic features of preadolescence LF and of AA during adolescence, along with their biological pathways and processes. Our study's primary medical significance lies in advancing the understanding of asthma's early life origins. By investigating epigenetic markers in newborns and their association with lung function in preadolescence, we aim to uncover potential early biomarkers of asthma risk. This could facilitate earlier detection and intervention strategies. Additionally, exploring biological pathways linking early lung function to later asthma development can offer insights into the disease's pathogenesis, potentially leading to novel therapeutic targets.</p><p><strong>Methods: </strong>The study was based on the Isle of Wight Birth cohort (IOWBC). Female subjects with DNAm data at birth and with no asthma at age 10 years were included (n = 249). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. Agreement in identified CpGs between AA and LF was examined, along with their biological pathways and processes via the R function gometh. We tested the findings in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine overall replicability.</p><p><strong>Results: </strong>In IOWBC, 292 CpGs were detected with DNAm associated with AA and 1517 unique CpGs for LF (514 for FEV1, 436 for FVC, 408 for FEV1/FVC), with one overlapping CpG, cg23642632 (<i>NCKAP1</i>) between AA and LF. Among the IOWBC-identified CpGs, we further tested in ALSPAC and observed the highest agreement between the two cohorts in FVC with respect to the direction of association and statistical significance. Epigenetic enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF.</p><p><strong>Conclusions: </strong>The present study suggests that FEV1, FVC, and FEV1/FVC (as objective measures of LF) and AA (incidence of asthma) are likely to have their own specific epigenetic features and biological pathways at birth. More replications are desirable to fully understand the complexity between DNAm, lung function, and asthma acquisition.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10961756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208300","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":"Dynamics and Epigenetics of the Epidermal Differentiation Complex.","authors":"Wiesława Leśniak","doi":"10.3390/epigenomes8010009","DOIUrl":"10.3390/epigenomes8010009","url":null,"abstract":"<p><p>Epidermis is the outer skin layer built of specialized cells called keratinocytes. Keratinocytes undergo a unique differentiation process, also known as cornification, during which their gene expression pattern, morphology and other properties change remarkably to the effect that the terminally differentiated, cornified cells can form a physical barrier, which separates the underlying tissues from the environment. Many genes encoding proteins that are important for epidermal barrier formation are located in a gene cluster called epidermal differentiation complex (EDC). Recent data provided valuable information on the dynamics of the EDC locus and the network of interactions between EDC gene promoters, enhancers and other regions, during keratinocytes differentiation. These data, together with results concerning changes in epigenetic modifications, provide a valuable insight into the mode of regulation of EDC gene expression.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10969700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295374","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":"Angio-Long Noncoding RNA MALAT1 (rs3200401) and MIAT (rs1061540) Gene Variants in Ovarian Cancer.","authors":"Manal S Fawzy, Afaf T Ibrahiem, Dalia Mohammad Osman, Amany I Almars, Maali Subhi Alshammari, Layan Tariq Almazyad, Noof Daif Allah Almatrafi, Renad Tariq Almazyad, Eman A Toraih","doi":"10.3390/epigenomes8010005","DOIUrl":"10.3390/epigenomes8010005","url":null,"abstract":"<p><p>The genotyping of long non-coding RNA (lncRNA)-related single-nucleotide polymorphisms (SNPs) could be associated with cancer risk and/or progression. This study aimed to analyze the angiogenesis-related lncRNAs MALAT1 (rs3200401) and MIAT (rs1061540) variants in patients with ovarian cancer (OC) using \"Real-Time allelic discrimination polymerase chain reaction\" in 182 formalin-fixed paraffin-embedded (FFPE) samples of benign, borderline, and primary malignant ovarian tissues. Differences in the genotype frequencies between low-grade ovarian epithelial tumors (benign/borderline) and malignant tumors and between high-grade malignant epithelial tumors and malignant epithelial tumors other than high-grade serous carcinomas were compared. Odds ratios (ORs)/95% confidence intervals were calculated as measures of the association strength. Additionally, associations of the genotypes with the available pathological data were analyzed. The heterozygosity of MALAT1 rs3200401 was the most common genotype (47.8%), followed by C/C (36.3%). Comparing the study groups, no significant differences were observed regarding this variant. In contrast, the malignant epithelial tumors had a higher frequency of the MIAT rs1061540 C/C genotype compared to the low-grade epithelial tumor cohorts (56.7% vs. 37.6, <i>p</i> = 0.031). The same genotype was significantly higher in high-grade serous carcinoma than its counterparts (69.4% vs. 43.8%, <i>p</i> = 0.038). Multivariate Cox regression analysis showed that the age at diagnosis was significantly associated with the risk of OC development. In contrast, the MIAT T/T genotype was associated with a low risk of malignant epithelial tumors under the homozygote comparison model (OR = 0.37 (0.16-0.83), <i>p</i> = 0.017). Also, MIAT T allele carriers were less likely to develop high-grade serous carcinoma under heterozygote (CT vs. CC; OR = 0.33 (0.12-0.88), <i>p</i> = 0.027) and homozygote (TT vs. CC; OR = 0.26 (0.07-0.90), <i>p</i> = 0.034) comparison models. In conclusion, our data provide novel evidence for a potential association between the lncRNA MIAT rs1061540 and the malignant condition of ovarian cancer, suggesting the involvement of such lncRNAs in OC development.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10885055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934462","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 Genomic Shock Hypothesis: Genetic and Epigenetic Alterations of Transposable Elements after Interspecific Hybridization in Plants.","authors":"Carlos de Tomás, Carlos M Vicient","doi":"10.3390/epigenomes8010002","DOIUrl":"10.3390/epigenomes8010002","url":null,"abstract":"<p><p>Transposable elements (TEs) are major components of plant genomes with the ability to change their position in the genome or to create new copies of themselves in other positions in the genome. These can cause gene disruption and large-scale genomic alterations, including inversions, deletions, and duplications. Host organisms have evolved a set of mechanisms to suppress TE activity and counter the threat that they pose to genome integrity. These includes the epigenetic silencing of TEs mediated by a process of RNA-directed DNA methylation (RdDM). In most cases, the silencing machinery is very efficient for the vast majority of TEs. However, there are specific circumstances in which TEs can evade such silencing mechanisms, for example, a variety of biotic and abiotic stresses or in vitro culture. Hybridization is also proposed as an inductor of TE proliferation. In fact, the discoverer of the transposons, Barbara McClintock, first hypothesized that interspecific hybridization provides a \"genomic shock\" that inhibits the TE control mechanisms leading to the mobilization of TEs. However, the studies carried out on this topic have yielded diverse results, showing in some cases a total absence of mobilization or being limited to only some TE families. Here, we review the current knowledge about the impact of interspecific hybridization on TEs in plants and the possible implications of changes in the epigenetic mechanisms.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"8 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10801548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514002","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}