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Advance in the Study of DNA Methylation 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 4621

Special Issue Editor


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Guest Editor
Chromatin and Aging Research Laboratory, Institute of Biomedical and Oral Sciences, Hebrew University of Jerusalem, Jerusalem, Israel
Interests: epigenetics; aging; histone modifications; DNA methylation; fertility; long-term starvation; evolutionary adaptation
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Special Issue Information

Dear Colleagues,

Over the last decade, research regarding topics related to DNA methylation has been developing and expanding. Currently, a description of cellular state is not complete without the complete characterization of the epigenome, of which the most commonly studied and most important aspect is DNA methylation. To advance the field even further, we offer this Special Issue of the IJMS, which will collect original research papers and reviews on topics related to DNA methylation as well as on the development of related research.

Dr. Michael Klutstein
Guest Editor

Manuscript Submission Information

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Keywords

  • DNA methylation
  • DMNT
  • TET
  • bisulfite sequencing
  • RRBS
  • epigenetics
  • aging
  • cancer

Published Papers (3 papers)

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Research

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19 pages, 8325 KiB  
Article
G6PD Orchestrates Genome-Wide DNA Methylation and Gene Expression in the Vascular Wall
by Christina Signoretti and Sachin A. Gupte
Int. J. Mol. Sci. 2023, 24(23), 16727; https://doi.org/10.3390/ijms242316727 - 24 Nov 2023
Cited by 1 | Viewed by 1031
Abstract
Recent advances have revealed the importance of epigenetic modifications to gene regulation and transcriptional activity. DNA methylation, a determinant of genetic imprinting and the de novo silencing of genes genome-wide, is known to be controlled by DNA methyltransferases (DNMT) and demethylases (TET) under [...] Read more.
Recent advances have revealed the importance of epigenetic modifications to gene regulation and transcriptional activity. DNA methylation, a determinant of genetic imprinting and the de novo silencing of genes genome-wide, is known to be controlled by DNA methyltransferases (DNMT) and demethylases (TET) under disease conditions. However, the mechanism(s)/factor(s) influencing the expression and activity of epigenetic writers and erasers, and thus DNA methylation, in healthy vascular tissue is incompletely understood. Based on our recent studies, we hypothesized that glucose-6-phosphate dehydrogenase (G6PD) is a modifier of DNMT and TET expression and activity and an enabler of gene expression. In the aorta of CRISPR-edited rats with the Mediterranean G6PD variant, we determined DNA methylation by whole-genome bisulfite sequencing, gene expression by RNA sequencing, and large artery stiffness by echocardiography. Here, we documented higher expression of Dnmt1, Dnmt3a, Tet2, and Tet3 in aortas from Mediterranean G6PDS188F variant (a loss-of-function single nucleotide polymorphism) rats than their wild-type littermates. Concomitantly, we identified 17,618 differentially methylated loci genome-wide (5787 hypermethylated loci, including down-regulated genes encoding inflammation- and vasoconstriction-causing proteins, and 11,827 hypomethylated loci, including up-regulated genes encoding smooth muscle cell differentiation- and fatty acid metabolism-promoting proteins) in aortas from G6PDS188F as compared to wild-type rats. Our results demonstrated that nitric oxide, which is generated in a G6PD-derived NADPH-dependent manner, increases TET and decreases DNMT activity. Further, we observed less large artery (aorta) stiffness in G6PDS188F as compared to wild-type rats. These results establish a noncanonical function of the wild-type G6PD and G6PDS188F variant in the regulation of DNA methylation and gene expression in healthy vascular tissue and reveal that the G6PDS188F variant contributes to reducing large artery stiffness. Full article
(This article belongs to the Special Issue Advance in the Study of DNA Methylation 2.0)
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16 pages, 1808 KiB  
Article
Genome-Wide DNA Methylation Profiles in Whole-Blood and Buccal Samples—Cross-Sectional, Longitudinal, and across Platforms
by Austin J. Van Asselt, Jeffrey J. Beck, Casey T. Finnicum, Brandon N. Johnson, Noah Kallsen, Jouke Jan Hottenga, Eco J. C. de Geus, BIOS Consortium, Dorret I. Boomsma, Erik A. Ehli and Jenny van Dongen
Int. J. Mol. Sci. 2023, 24(19), 14640; https://doi.org/10.3390/ijms241914640 - 27 Sep 2023
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Abstract
The field of DNA methylation research is rapidly evolving, focusing on disease and phenotype changes over time using methylation measurements from diverse tissue sources and multiple array platforms. Consequently, identifying the extent of longitudinal, inter-tissue, and inter-platform variation in DNA methylation is crucial [...] Read more.
The field of DNA methylation research is rapidly evolving, focusing on disease and phenotype changes over time using methylation measurements from diverse tissue sources and multiple array platforms. Consequently, identifying the extent of longitudinal, inter-tissue, and inter-platform variation in DNA methylation is crucial for future advancement. DNA methylation was measured in 375 individuals, with 197 of those having 2 blood sample measurements ~10 years apart. Whole-blood samples were measured on Illumina Infinium 450K and EPIC methylation arrays, and buccal samples from a subset of 58 participants were measured on EPIC array. The data were analyzed with the aims to examine the correlation between methylation levels in longitudinal blood samples in 197 individuals, examine the correlation between methylation levels in the blood and buccal samples in 58 individuals, and examine the correlation between blood methylation profiles assessed on the EPIC and 450K arrays in 83 individuals. We identified 136,833, 7674, and 96,891 CpGs significantly and strongly correlated (>0.50) longitudinally, across blood and buccal samples as well as array platforms, respectively. A total of 3674 of these CpGs were shared across all three sets. Analysis of these shared CpGs identified previously found associations with aging, ancestry, and 7016 mQTLs as well. Full article
(This article belongs to the Special Issue Advance in the Study of DNA Methylation 2.0)
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Review

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18 pages, 791 KiB  
Review
DNA Methylation in the Fields of Prenatal Diagnosis and Early Detection of Cancers
by Fabio Coppedè, Utsa Bhaduri, Andrea Stoccoro, Vanessa Nicolì, Eleonora Di Venere and Giuseppe Merla
Int. J. Mol. Sci. 2023, 24(14), 11715; https://doi.org/10.3390/ijms241411715 - 20 Jul 2023
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Abstract
The central objective of the metamorphosis of discovery science into biomedical applications is to serve the purpose of patients and curtail the global disease burden. The journey from the discovery of DNA methylation (DNAm) as a biological process to its emergence as a [...] Read more.
The central objective of the metamorphosis of discovery science into biomedical applications is to serve the purpose of patients and curtail the global disease burden. The journey from the discovery of DNA methylation (DNAm) as a biological process to its emergence as a diagnostic tool is one of the finest examples of such metamorphosis and has taken nearly a century. Particularly in the last decade, the application of DNA methylation studies in the clinic has been standardized more than ever before, with great potential to diagnose a multitude of diseases that are associated with a burgeoning number of genes with this epigenetic alteration. Fetal DNAm detection is becoming useful for noninvasive prenatal testing, whereas, in very preterm infants, DNAm is also shown to be a potential biological indicator of prenatal risk factors. In the context of cancer, liquid biopsy-based DNA-methylation profiling is offering valuable epigenetic biomarkers for noninvasive early-stage diagnosis. In this review, we focus on the applications of DNA methylation in prenatal diagnosis for delivering timely therapy before or after birth and in detecting early-stage cancers for better clinical outcomes. Furthermore, we also provide an up-to-date commercial landscape of DNAm biomarkers for cancer detection and screening of cancers of unknown origin. Full article
(This article belongs to the Special Issue Advance in the Study of DNA Methylation 2.0)
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