EpigenomesPub Date : 2023-01-13DOI: 10.3390/epigenomes7010003
Epigenomes Editorial Office
{"title":"Acknowledgment to the Reviewers of <i>Epigenomes</i> in 2022.","authors":"Epigenomes Editorial Office","doi":"10.3390/epigenomes7010003","DOIUrl":"https://doi.org/10.3390/epigenomes7010003","url":null,"abstract":"<p><p>High-quality academic publishing is built on rigorous peer review [...].</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547892","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}
EpigenomesPub Date : 2023-01-10DOI: 10.3390/epigenomes7010002
Elena Tomeva, Ulrike D B Krammer, Olivier J Switzeny, Alexander G Haslberger, Berit Hippe
{"title":"Sex-Specific miRNA Differences in Liquid Biopsies from Subjects with Solid Tumors and Healthy Controls.","authors":"Elena Tomeva, Ulrike D B Krammer, Olivier J Switzeny, Alexander G Haslberger, Berit Hippe","doi":"10.3390/epigenomes7010002","DOIUrl":"https://doi.org/10.3390/epigenomes7010002","url":null,"abstract":"<p><p>Dysregulation of epigenetic mechanisms has been recognized to play a crucial role in cancer development, but these mechanisms vary between sexes. Therefore, we focused on sex-specific differences in the context of cancer-based data from a recent study. A total of 12 cell-free DNA methylation targets in CpG-rich promoter regions and 48 miRNAs were analyzed by qPCR in plasma samples from 8 female and 7 male healthy controls as well as 48 female and 80 male subjects with solid tumors of the bladder, brain, colorectal region (CRC), lung, stomach, pancreas, and liver. Due to the small sample size in some groups and/or the non-balanced distribution of men and women, sex-specific differences were evaluated statistically only in healthy subjects, CRC, stomach or pancreas cancer patients, and all cancer subjects combined (<i>n</i> female/male-8/7, 14/14, 8/15, 6/6, 48/80, respectively). Several miRNAs with opposing expressions between the sexes were observed for healthy subjects (miR-17-5p, miR-26b-5p); CRC patients (miR-186-5p, miR-22-3p, miR-22-5p, miR-25-3p, miR-92a-3p, miR-16-5p); stomach cancer patients (miR-133a-3p, miR-22-5p); and all cancer patients combined (miR-126-3p, miR-21-5p, miR-92a-3p, miR-183-5p). Moreover, sex-specific correlations that were dependent on cancer stage were observed in women (miR-27a-3p) and men (miR-17-5p, miR-20a-5p). Our results indicate the complex and distinct role of epigenetic regulation, particularly miRNAs, depending not only on the health status but also on the sex of the patient. The same miRNAs could have diverse effects in different tissues and opposing effects between the biological sexes, which should be considered in biomarker research.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10547893","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}
EpigenomesPub Date : 2022-12-26DOI: 10.3390/epigenomes7010001
Günter Vogt
{"title":"Environmental Adaptation of Genetically Uniform Organisms with the Help of Epigenetic Mechanisms-An Insightful Perspective on Ecoepigenetics.","authors":"Günter Vogt","doi":"10.3390/epigenomes7010001","DOIUrl":"10.3390/epigenomes7010001","url":null,"abstract":"<p><p>Organisms adapt to different environments by selection of the most suitable phenotypes from the standing genetic variation or by phenotypic plasticity, the ability of single genotypes to produce different phenotypes in different environments. Because of near genetic identity, asexually reproducing populations are particularly suitable for the investigation of the potential and molecular underpinning of the latter alternative in depth. Recent analyses on the whole-genome scale of differently adapted clonal animals and plants demonstrated that epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNAs are among the molecular pathways supporting phenotypic plasticity and that epigenetic variation is used to stably adapt to different environments. Case studies revealed habitat-specific epigenetic fingerprints that were maintained over subsequent years pointing at the existence of epigenetic ecotypes. Environmentally induced epimutations and corresponding gene expression changes provide an ideal means for fast and directional adaptation to changing or new conditions, because they can synchronously alter phenotypes in many population members. Because microorganisms inclusive of human pathogens also exploit epigenetically mediated phenotypic variation for environmental adaptation, this phenomenon is considered a universal biological principle. The production of different phenotypes from the same DNA sequence in response to environmental cues by epigenetic mechanisms also provides a mechanistic explanation for the \"general-purpose genotype hypothesis\" and the \"genetic paradox of invasions\".</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"7 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9184363","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}
EpigenomesPub Date : 2022-12-09DOI: 10.3390/epigenomes6040043
Kenneth C Ehrlich, Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan, Melanie Ehrlich
{"title":"Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: <i>TBX15</i> in the Muscle Lineage.","authors":"Kenneth C Ehrlich, Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan, Melanie Ehrlich","doi":"10.3390/epigenomes6040043","DOIUrl":"https://doi.org/10.3390/epigenomes6040043","url":null,"abstract":"<p><p>TBX15, which encodes a differentiation-related transcription factor, displays promoter-adjacent DNA hypermethylation in myoblasts and skeletal muscle (psoas) that is absent from non-expressing cells in other lineages. By whole-genome bisulfite sequencing (WGBS) and enzymatic methyl-seq (EM-seq), these hypermethylated regions were found to border both sides of a constitutively unmethylated promoter. To understand the functionality of this DNA hypermethylation, we cloned the differentially methylated sequences (DMRs) in CpG-free reporter vectors and tested them for promoter or enhancer activity upon transient transfection. These cloned regions exhibited strong promoter activity and, when placed upstream of a weak promoter, strong enhancer activity specifically in myoblast host cells. In vitro CpG methylation targeted to the DMR sequences in the plasmids resulted in 86−100% loss of promoter or enhancer activity, depending on the insert sequence. These results as well as chromatin epigenetic and transcription profiles for this gene in various cell types support the hypothesis that DNA hypermethylation immediately upstream and downstream of the unmethylated promoter region suppresses enhancer/extended promoter activity, thereby downmodulating, but not silencing, expression in myoblasts and certain kinds of skeletal muscle. This promoter-border hypermethylation was not found in cell types with a silent TBX15 gene, and these cells, instead, exhibit repressive chromatin in and around the promoter. TBX18, TBX2, TBX3 and TBX1 display TBX15-like hypermethylated DMRs at their promoter borders and preferential expression in myoblasts. Therefore, promoter-adjacent DNA hypermethylation for downmodulating transcription to prevent overexpression may be used more frequently for transcription regulation than currently appreciated.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082504","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}
EpigenomesPub Date : 2022-12-02DOI: 10.3390/epigenomes6040042
Lucy Anne Doyle, Firuze Unlu Bektas, Eleftheria Chatzantonaki, Charlotte Repton, Alexandra Derrien, Robert Scott Illingworth
{"title":"RINGs, DUBs and Abnormal Brain Growth-Histone H2A Ubiquitination in Brain Development and Disease.","authors":"Lucy Anne Doyle, Firuze Unlu Bektas, Eleftheria Chatzantonaki, Charlotte Repton, Alexandra Derrien, Robert Scott Illingworth","doi":"10.3390/epigenomes6040042","DOIUrl":"https://doi.org/10.3390/epigenomes6040042","url":null,"abstract":"<p><p>During mammalian neurodevelopment, signaling pathways converge upon transcription factors (TFs) to establish appropriate gene expression programmes leading to the production of distinct neural and glial cell types. This process is partially regulated by the dynamic modulation of chromatin states by epigenetic systems, including the polycomb group (PcG) family of co-repressors. PcG proteins form multi-subunit assemblies that sub-divide into distinct, yet functionally related families. Polycomb repressive complexes 1 and 2 (PRC1 and 2) modify the chemical properties of chromatin by covalently modifying histone tails via H2A ubiquitination (H2AK119ub1) and H3 methylation, respectively. In contrast to the PRCs, the Polycomb repressive deubiquitinase (PR-DUB) complex removes H2AK119ub1 from chromatin through the action of the C-terminal hydrolase BAP1. Genetic screening has identified several PcG mutations that are causally associated with a range of congenital neuropathologies associated with both localised and/or systemic growth abnormalities. As PRC1 and PR-DUB hold opposing functions to control H2AK119ub1 levels across the genome, it is plausible that such neurodevelopmental disorders arise through a common mechanism. In this review, we will focus on advancements regarding the composition and opposing molecular functions of mammalian PRC1 and PR-DUB, and explore how their dysfunction contributes to the emergence of neurodevelopmental disorders.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10771806","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}
EpigenomesPub Date : 2022-11-28DOI: 10.3390/epigenomes6040041
Xiaodong Liu, Xiao-Jiang Li, Li Lin
{"title":"Dynamic 5-Hydroxymethylcytosine Change: Implication for Aging of Non-Human Primate Brain.","authors":"Xiaodong Liu, Xiao-Jiang Li, Li Lin","doi":"10.3390/epigenomes6040041","DOIUrl":"https://doi.org/10.3390/epigenomes6040041","url":null,"abstract":"<p><p>Profiling of 5-hydroxymethylcytosine (5hmC) in the brain regions of rhesus monkey at different ages reveals accumulation and tissue-specific patterns of 5hmC with aging. Region-specific differentially hydroxymethylated regions (DhMRs) are involved in neuronal functions and signal transduction. These data suggest that 5hmC may be a key regulator of gene transcription in neurodevelopment and thus a potential candidate for the epigenetic clock. Importantly, non-human primates are the ideal animal models for investigation of human aging and diseases not only because they are more genetically similar to humans but also epigenetically.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414054","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}
EpigenomesPub Date : 2022-11-03DOI: 10.3390/epigenomes6040040
Ibani Kapur, Elodie L Boulier, Nicole J Francis
{"title":"Regulation of Polyhomeotic Condensates by Intrinsically Disordered Sequences That Affect Chromatin Binding.","authors":"Ibani Kapur, Elodie L Boulier, Nicole J Francis","doi":"10.3390/epigenomes6040040","DOIUrl":"https://doi.org/10.3390/epigenomes6040040","url":null,"abstract":"<p><p>The Polycomb group (PcG) complex PRC1 localizes in the nucleus in condensed structures called Polycomb bodies. The PRC1 subunit Polyhomeotic (Ph) contains an oligomerizing sterile alpha motif (SAM) that is implicated in both PcG body formation and chromatin organization in <i>Drosophila</i> and mammalian cells. A truncated version of Ph containing the SAM (mini-Ph) forms phase-separated condensates with DNA or chromatin in vitro, suggesting that PcG bodies may form through SAM-driven phase separation. In cells, Ph forms multiple small condensates, while mini-Ph typically forms a single large nuclear condensate. We therefore hypothesized that sequences outside of mini-Ph, which are predicted to be intrinsically disordered, are required for proper condensate formation. We identified three distinct low-complexity regions in Ph based on sequence composition. We systematically tested the role of each of these sequences in Ph condensates using live imaging of transfected <i>Drosophila</i> S2 cells. Each sequence uniquely affected Ph SAM-dependent condensate size, number, and morphology, but the most dramatic effects occurred when the central, glutamine-rich intrinsically disordered region (IDR) was removed, which resulted in large Ph condensates. Like mini-Ph condensates, condensates lacking the glutamine-rich IDR excluded chromatin. Chromatin fractionation experiments indicated that the removal of the glutamine-rich IDR reduced chromatin binding and that the removal of either of the other IDRs increased chromatin binding. Our data suggest that all three IDRs, and functional interactions among them, regulate Ph condensate size and number. Our results can be explained by a model in which tight chromatin binding by Ph IDRs antagonizes Ph SAM-driven phase separation. Our observations highlight the complexity of regulation of biological condensates housed in single proteins.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318017","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}
EpigenomesPub Date : 2022-11-03DOI: 10.3390/epigenomes6040039
Shivangi Shukla, Ashutosh Kumar
{"title":"Centromere Chromatin Dynamics at a Glance.","authors":"Shivangi Shukla, Ashutosh Kumar","doi":"10.3390/epigenomes6040039","DOIUrl":"https://doi.org/10.3390/epigenomes6040039","url":null,"abstract":"The centromere is a specialized DNA locus that ensures the faithful segregation of chromosomes during cell division. It does so by directing the assembly of an essential proteinaceous structure called the kinetochore. The centromere identity is primarily epigenetically defined by a nucleosome containing an H3 variant called CENP-A as well as by the interplay of several factors such as differential chromatin organization driven by CENP-A and H2A.Z, centromere-associated proteins, and post-translational modifications. At the centromere, CENP-A is not just a driving force for kinetochore assembly but also modifies the structural and dynamic properties of the centromeric chromatin, resulting in a distinctive chromatin organization. An additional level of regulation of the centromeric chromatin conformation is provided by post-translational modifications of the histones in the CENP-A nucleosomes. Further, H2A.Z is present in the regions flanking the centromere for heterochromatinization. In this review, we focus on the above-mentioned factors to describe how they contribute to the organization of the centromeric chromatin: CENP-A at the core centromere, post-translational modifications that decorate CENP-A, and the variant H2A.Z.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10322684","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}
EpigenomesPub Date : 2022-11-03DOI: 10.3390/epigenomes6040038
Ubah Dominic Babah Ubah, Korawin Triyasakorn, Brandon Roan, Minsyusheen Conlin, James C K Lai, Prabha S Awale
{"title":"Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages.","authors":"Ubah Dominic Babah Ubah, Korawin Triyasakorn, Brandon Roan, Minsyusheen Conlin, James C K Lai, Prabha S Awale","doi":"10.3390/epigenomes6040038","DOIUrl":"https://doi.org/10.3390/epigenomes6040038","url":null,"abstract":"This study was initiated as an attempt to clarify some of the apparent conflicting data regarding the so-called anti-inflammatory versus proinflammatory properties of histone deacetylase inhibitors (HDACis). In cell culture, typically, chronic pretreatment with the HDACi valproic acid (VPA) and trichostatin A (TSA) exhibits an anti-inflammatory effect. However, the effect of acute treatment with VPA and TSA on the levels of inflammatory cytokines in J774A.1 macrophage cell line is unknown. Therefore, this study investigated the effect of acute treatment with VPA and TSA on levels of key inflammatory cytokines in maximally stimulated J774A.1 cells. J774A.1 macrophages were treated with either VPA or TSA for 1 h (acute treatment), followed by maximal stimulation with LPS + IFNγ for 24 h. ELISA was used to measure the levels of proinflammatory cytokines TNFα, NO and IL-1β from the culture medium. Acute treatment with VPA showed a dose-dependent increase in levels of all three cytokines. Similar to VPA, TSA also showed a dose-dependent increase in levels of IL-1β alone. This study sheds new light on the conflicting data in the literature that may partly be explained by acute or short-term exposure versus chronic or long-term exposure to HDACi.","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9680436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318023","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":"Modulation of DNA Methylation/Demethylation Reactions Induced by Nutraceuticals and Pollutants of Exposome Can Promote a C > T Mutation in the Breast Cancer Predisposing Gene PALB2","authors":"Florestan Courant, Gwenola Bougras-Cartron, Caroline Abadie, Jean-Sébastien Frenel, Pierre-François Cartron","doi":"10.3390/epigenomes6040032","DOIUrl":"https://doi.org/10.3390/epigenomes6040032","url":null,"abstract":"<p><p>Background: Deregulation of DNA methylation/demethylation reactions may be the source of C > T mutation via active deamination of 5-methylcytosine to thymine. Exposome, that is to say, the totality of exposures to which an individual is subjected during their life, can deregulate these reactions. Thus, one may wonder whether the exposome can induce C > T mutations in the breast cancer-predisposing gene PALB2. Methods: Our work is based on the exposure of MCF10A mammary epithelial cells to seven compounds of our exposome (folate, Diuron, glyphosate, PFOA, iron, zinc, and ascorbic acid) alone or in cocktail. The qMSRE and RMS techniques were used to study the impact of these exposures on the level of methylation and mutation of the PALB2 gene. Results: Here, we have found that exposome compounds (nutriments, ions, pollutants) promoting the cytosine methylation and the 5-methylcytosine deamination have the ability to promote a specific C > T mutation in the PALB2 gene. Interestingly, we also noted that the addition of exposome compounds promoting the TET-mediated conversion of 5-methylcytosine (Ascorbic acid and iron) abrogates the presence of C > T mutation in the PALB2 gene. Conclusions: Our study provides a proof of concept supporting the idea that exposomes can generate genetic mutation by affecting DNA methylation/demethylation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"6 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9590087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127105","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}