Epigenomes

17 pages, 1840 KiB

Open AccessArticle

Epigenomic Interactions Between Chronic Pain and Recurrent Pressure Injuries After Spinal Cord Injury

by Letitia Y. Graves, Melissa R. Alcorn, E. Ricky Chan, Katelyn Schwartz, M. Kristi Henzel, Marinella Galea, Anna M. Toth, Christine M. Olney and Kath M. Bogie

Epigenomes 2025, 9(3), 26; https://doi.org/10.3390/epigenomes9030026 - 23 Jul 2025

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Abstract

Background/Objectives: This study investigated variations in DNA methylation patterns associated with chronic pain and propensity for recurrent pressure injuries (PrI) in persons with spinal cord injury (SCI). Methods: Whole blood was collected from 81 individuals with SCI. DNA methylation was quantified using Illumina genome-wide arrays (EPIC and EPICv2). Comprehensive clinical profiles collected included secondary health complications, in particular current PrI and chronic pain. Relationships between recurrent PrI and chronic pain and whether the co-occurrence of both traits was mediated by changes in DNA methylation were investigated using R packages limma, DMRcate and mCSEA. Results: Three differentially methylated positions (DMPs) (cg09867095, cg26559694, cg24890286) and one region in the micro-imprinted locus for BLCAP/NNAT are associated with chronic pain in persons with SCI. The study cohort was stratified by PrI status to identify any sites associated with chronic pain and while the same three sites and region were replicated in the group with no recurrent PrI, two novel, hypermethylated (cg21756558, cg26217441) sites and one region in the protein-coding gene FDFT1 were identified in the group with recurrent PrI. Gene enrichment and genes associated with specific promoters using MetaScape identified several shared disorders and ontology terms between independent phenotypes of pain and recurrent PrI and interactive sub-groups. Conclusions: DMR analysis using mCSEA identified several shared genes, promoter-associated regions and CGI associated with overall pain and PrI history, as well as sub-groups based on recurrent PrI history. These findings suggest that a much larger gene regulatory network is associated with each phenotype. These findings require further validation. Full article

(This article belongs to the Special Issue Features Papers in Epigenomes 2025)

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17 pages, 6145 KiB

Open AccessArticle

Exploring Epigenetic Ageing Using Direct Methylome Sequencing

by Elena-Cristina Găitănaru, Roua Gabriela Popescu, Andreea-Angelica Stroe, Sergiu Emil Georgescu and George Cătălin Marinescu

Epigenomes 2025, 9(3), 25; https://doi.org/10.3390/epigenomes9030025 - 14 Jul 2025

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Abstract

Background/Objectives: Advances in nanopore sequencing have opened new avenues for studying DNA methylation at single-base resolution, yet their application in epigenetic ageing research remains underdeveloped. Methods: We present a novel framework that leverages the unique capabilities of nanopore sequencing to profile and interpret age-associated methylation patterns in native DNA. Results: Unlike conventional array-based approaches, long reads sequencing captures full CpG context, accommodates diverse and repetitive genomic regions, removes bisulfite conversion steps, and is compatible to the latest reference genome. Conclusions: This work establishes nanopore sequencing as a powerful tool for next-generation epigenetic ageing studies, offering a scalable and biologically rich platform for anti-ageing interventions monitoring and longitudinal ageing studies. Full article

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24 pages, 2421 KiB

Open AccessArticle

Trends in DNA Methylation over Time Between Parous and Nulliparous Young Women

by Su Chen, John W. Holloway, Wilfried Karmaus, Hongmei Zhang, S. Hasan Arshad and Susan Ewart

Epigenomes 2025, 9(3), 24; https://doi.org/10.3390/epigenomes9030024 - 10 Jul 2025

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Abstract

Background/Objectives: The experience of pregnancy and parturition has been associated with long-term health effects in mothers, imparting protective effects against some diseases while the risk of other diseases is increased. The mechanisms that drive these altered disease risks are unknown. This study examined DNA methylation (DNAm) changes from pre-pregnancy to several years after giving birth in parous women compared to nulliparous controls over the same time interval. Methods: Using 180 parous-associated CpGs, three analyses were carried out to test DNAm changes from pre-pregnancy at age 18 years to gestation; from gestation to post-pregnancy at age 26 years in parous women; and from 18 to 26 years in nulliparous women using linear mixed models with repeated measures. Results: The directions of DNAm changes were the same between the parous and nulliparous groups. Most CpG dinucleotides (67%, 121 of 180) had a decreasing trend while a small number (7%, 13 of 180) had an increasing trend. Of the CpGs showing increasing or decreasing DNAm, approximately half had DNAm change to a smaller extent in parous women and the other half changed more in parous women than nulliparous controls. 9% (17 of 180) changed significantly in nulliparous women only, leading to a significant difference in DNAm levels in parous women at the post-pregnancy 26 years time point. Conclusions: Pregnancy and parturition may accelerate methylation changes in some CpGs, but slow down or halt methylation changes over time in other CpGs. Full article

(This article belongs to the Special Issue Longitudinal Studies on Prenatal or Early Life Exposures, Their Associated Epigenetics, and Population Health)

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17 pages, 532 KiB

Open AccessReview

The Fundamental Role of Nutrients for Metabolic Balance and Epigenome Integrity Maintenance

by Ana Paula de Souza, Vitor Marinho and Marcelo Rocha Marques

Epigenomes 2025, 9(3), 23; https://doi.org/10.3390/epigenomes9030023 - 9 Jul 2025

Viewed by 364

Abstract

Epigenetic modifications act as crucial regulators of gene activity and are influenced by both internal and external environmental factors, with diet being the most impactful external factor. On the other hand, cellular metabolism encompasses a complex network of biochemical reactions essential for maintaining cellular function, and it impacts every cellular process. Many metabolic cofactors are critical for the activity of chromatin-modifying enzymes, influencing methylation and the global acetylation status of the epigenome. For instance, dietary nutrients, particularly those involved in one-carbon metabolism (e.g., folate, vitamins B12 and B6, riboflavin, methionine, choline, and betaine), take part in the generation of S-adenosylmethionine (SAM), which represents the main methyl donor for DNA and histone methylation; α-ketoglutarate and ascorbic acid (vitamin C) act, respectively, as a co-substrate and cofactor for Ten-eleven Translocation (TET), which is responsible for DNA demethylation; and metabolites such as Acetyl-CoA directly impact histone acetylation, linking metabolism of the TCA cycle to epigenetic regulation. Further, bioactive compounds, such as polyphenols, modulate epigenetic patterns by affecting methylation processes or targeting epigenetic enzymes. Since diet and nutrition play a critical role in shaping epigenome functions and supporting human health, this review offers a comprehensive update on recent advancements in metabolism, epigenetics, and nutrition, providing insights into how nutrients contribute to metabolic balance, epigenome integrity maintenance and, consequently, disease prevention. Full article

(This article belongs to the Collection Feature Papers in Epigenomes)

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Epigenomes, Volume 9, Issue 3 (September 2025) – 4 articles

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