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Epigenomes, Volume 5, Issue 3 (September 2021) – 4 articles

Cover Story (view full-size image): Cancer progression recapitulates several features of the placenta by hijacking epigenetic regulators and gene expression patterns involved in cell identity and differentiation. The hypomethylation of repetitive DNA sequences is a common phenomenon shared between cancer and the placenta, which is able to cause the activation of sequences involved in hallmark processes, such as invasiveness, immune response and inflammation. In both the placenta and cancer, reactivated repetitive sequences can influence gene splicing, enhancer and promoter functions, and the expression of these early developmental genes could help us to identify new molecules for cancer treatment, and potentially provide new insights into cancer immunotherapy resistance. View this paper
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Review
Evolution of CG Methylation Maintenance Machinery in Plants
Epigenomes 2021, 5(3), 19; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5030019 - 14 Sep 2021
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Abstract
Cytosine methylation is an epigenetic mark present in most eukaryotic genomes that contributes to the regulation of gene expression and the maintenance of genome stability. DNA methylation mostly occurs at CG sequences, where it is initially deposited by de novo DNA methyltransferases and [...] Read more.
Cytosine methylation is an epigenetic mark present in most eukaryotic genomes that contributes to the regulation of gene expression and the maintenance of genome stability. DNA methylation mostly occurs at CG sequences, where it is initially deposited by de novo DNA methyltransferases and propagated by maintenance DNA methyltransferases (DNMT) during DNA replication. In this review, we first summarize the mechanisms maintaining CG methylation in mammals that involve the DNA Methyltransferase 1 (DNMT1) enzyme and its cofactor, UHRF1 (Ubiquitin-like with PHD and RING Finger domain 1). We then discuss the evolutionary conservation and diversification of these two core factors in the plant kingdom and speculate on potential functions of novel homologues typically observed in land plants but not in mammals. Full article
(This article belongs to the Special Issue Mechanisms of Plant Epigenome Dynamics)
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Article
Epigenetic Analyses of Alcohol Consumption in Combustible and Non-Combustible Nicotine Product Users
Epigenomes 2021, 5(3), 18; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5030018 - 01 Sep 2021
Viewed by 535
Abstract
Alcohol and tobacco use are highly comorbid and exacerbate the associated morbidity and mortality of either substance alone. However, the relationship of alcohol consumption to the various forms of nicotine-containing products is not well understood. To improve this understanding, we examined the relationship [...] Read more.
Alcohol and tobacco use are highly comorbid and exacerbate the associated morbidity and mortality of either substance alone. However, the relationship of alcohol consumption to the various forms of nicotine-containing products is not well understood. To improve this understanding, we examined the relationship of alcohol consumption to nicotine product use using self-report, cotinine, and two epigenetic biomarkers specific for smoking (cg05575921) and drinking (Alcohol T Scores (ATS)) in n = 424 subjects. Cigarette users had significantly higher ATS values than the other groups (p < 2.2 × 10−16). Using the objective biomarkers, the intensity of nicotine and alcohol consumption was correlated in both the cigarette and smokeless users (R = −0.66, p = 3.1 × 10−14; R2 = 0.61, p = 1.97 × 10−4). Building upon this idea, we used the objective nicotine biomarkers and age to build and test a Balanced Random Forest classification model for heavy alcohol consumption (ATS > 2.35). The model performed well with an AUC of 0.962, 89.3% sensitivity, and 85% specificity. We conclude that those who use non-combustible nicotine products drink significantly less than smokers, and cigarette and smokeless users drink more with heavier nicotine use. These findings further highlight the lack of informativeness of self-reported alcohol consumption and suggest given the public and private health burden of alcoholism, further research into whether using non-combustible nicotine products as a mode of treatment for dual users should be considered. Full article
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Review
Deciphering Plant Chromatin Regulation via CRISPR/dCas9-Based Epigenome Engineering
Epigenomes 2021, 5(3), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5030017 - 24 Aug 2021
Viewed by 612
Abstract
CRISPR-based epigenome editing uses dCas9 as a platform to recruit transcription or chromatin regulators at chosen loci. Despite recent and ongoing advances, the full potential of these approaches to studying chromatin functions in vivo remains challenging to exploit. In this review we discuss [...] Read more.
CRISPR-based epigenome editing uses dCas9 as a platform to recruit transcription or chromatin regulators at chosen loci. Despite recent and ongoing advances, the full potential of these approaches to studying chromatin functions in vivo remains challenging to exploit. In this review we discuss how recent progress in plants and animals provides new routes to investigate the function of chromatin regulators and address the complexity of associated regulations that are often interconnected. While efficient transcriptional engineering methodologies have been developed and can be used as tools to alter the chromatin state of a locus, examples of direct manipulation of chromatin regulators remain scarce in plants. These reports also reveal pitfalls and limitations of epigenome engineering approaches that are nevertheless informative as they are often associated with locus- and context-dependent features, which include DNA accessibility, initial chromatin and transcriptional state or cellular dynamics. Strategies implemented in different organisms to overcome and even take advantage of these limitations are highlighted, which will further improve our ability to establish the causality and hierarchy of chromatin dynamics on genome regulation. Full article
(This article belongs to the Special Issue Mechanisms of Plant Epigenome Dynamics)
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Review
Can Immune Suppression and Epigenome Regulation in Placenta Offer Novel Insights into Cancer Immune Evasion and Immunotherapy Resistance?
Epigenomes 2021, 5(3), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/epigenomes5030016 - 25 Jul 2021
Viewed by 870
Abstract
Cancer is the second leading cause of mortality and morbidity in the developed world. Cancer progression involves genetic and epigenetic alterations, accompanied by aggressive changes, such as increased immune evasion, onset of metastasis, and drug resistance. Similar to cancer, DNA hypomethylation, immune suppression, [...] Read more.
Cancer is the second leading cause of mortality and morbidity in the developed world. Cancer progression involves genetic and epigenetic alterations, accompanied by aggressive changes, such as increased immune evasion, onset of metastasis, and drug resistance. Similar to cancer, DNA hypomethylation, immune suppression, and invasive cell behaviours are also observed in the human placenta. Mechanisms that lead to the acquisition of invasive behaviour, immune evasion, and drug and immunotherapy resistance are presently under intense investigations to improve patient outcomes. Here, we review current knowledge regarding the similarities between immune suppression and epigenome regulation, including the expression of repetitive elements (REs), endogenous retroviruses (ERVs) and transposable elements (TEs) in cells of the placenta and in cancer, which are associated with changes in immune regulation and invasiveness. We explore whether immune suppression and epigenome regulation in placenta offers novel insights into immunotherapy resistance in cancer, and we also discuss the implications and the knowledge gaps relevant to these findings, which are rapidly being accrued in these quite disparate research fields. Finally, we discuss potential linkages between TE, ERV and RE activation and expression, regarding mechanisms of immune regulation in placenta and cancer. A greater understanding of the role of immune suppression and associated epigenome regulation in placenta could help to elucidate some comparable mechanisms operating in cancer, and identify potential new therapeutic targets for treating cancer. Full article
(This article belongs to the Special Issue Epigenetics and Immune Checkpoints)
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