Recent Advances in Biological Methylation 2022

A special issue of Epigenomes (ISSN 2075-4655).

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 8303

Special Issue Editor


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Guest Editor
Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, NY 10029, USA
Interests: methyltransferases; transcription; splicing; cancer; genomics
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Special Issue Information

Dear Colleagues, 

The dynamics of histone methylation/demethylation (both on arginines and lysines) and of RNA epitranscriptomics have recently emerged as two of the most exciting areas of study in transcriptional and post-transcriptional regulation. In this Special Issue, we welcome the submission of both reviews and original papers broadly dealing with advances in the field of biological methylation. 

This Special Issue is related to The Biological Methylation Conference: Fundamental Mechanisms in Human Health and Disease taking place from June 19–23, 2022 at Catania, Italy. 

Prof. Dr. Ernesto Guccione
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Epigenomes is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (3 papers)

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Research

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25 pages, 1507 KiB  
Article
Promoter-Adjacent DNA Hypermethylation Can Downmodulate Gene Expression: TBX15 in the Muscle Lineage
by Kenneth C. Ehrlich, Michelle Lacey, Carl Baribault, Sagnik Sen, Pierre Olivier Esteve, Sriharsa Pradhan and Melanie Ehrlich
Epigenomes 2022, 6(4), 43; https://doi.org/10.3390/epigenomes6040043 - 09 Dec 2022
Cited by 2 | Viewed by 2961
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Advances in Biological Methylation 2022)
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Review

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19 pages, 1096 KiB  
Review
Histone Demethylase Modulation: Epigenetic Strategy to Combat Cancer Progression
by Rashmi Srivastava, Rubi Singh, Shaurya Jauhari, Niraj Lodhi and Rakesh Srivastava
Epigenomes 2023, 7(2), 10; https://doi.org/10.3390/epigenomes7020010 - 17 May 2023
Cited by 1 | Viewed by 2798
Abstract
Epigenetic modifications are heritable, reversible changes in histones or the DNA that control gene functions, being exogenous to the genomic sequence itself. Human diseases, particularly cancer, are frequently connected to epigenetic dysregulations. One of them is histone methylation, which is a dynamically reversible [...] Read more.
Epigenetic modifications are heritable, reversible changes in histones or the DNA that control gene functions, being exogenous to the genomic sequence itself. Human diseases, particularly cancer, are frequently connected to epigenetic dysregulations. One of them is histone methylation, which is a dynamically reversible and synchronously regulated process that orchestrates the three-dimensional epigenome, nuclear processes of transcription, DNA repair, cell cycle, and epigenetic functions, by adding or removing methylation groups to histones. Over the past few years, reversible histone methylation has become recognized as a crucial regulatory mechanism for the epigenome. With the development of numerous medications that target epigenetic regulators, epigenome-targeted therapy has been used in the treatment of malignancies and has shown meaningful therapeutic potential in preclinical and clinical trials. The present review focuses on the recent advances in our knowledge on the role of histone demethylases in tumor development and modulation, in emphasizing molecular mechanisms that control cancer cell progression. Finally, we emphasize current developments in the advent of new molecular inhibitors that target histone demethylases to regulate cancer progression. Full article
(This article belongs to the Special Issue Recent Advances in Biological Methylation 2022)
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Other

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3 pages, 176 KiB  
Commentary
Dynamic 5-Hydroxymethylcytosine Change: Implication for Aging of Non-Human Primate Brain
by Xiaodong Liu, Xiao-Jiang Li and Li Lin
Epigenomes 2022, 6(4), 41; https://doi.org/10.3390/epigenomes6040041 - 28 Nov 2022
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Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Advances in Biological Methylation 2022)
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