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Epigenomes

Epigenomes is an international, peer-reviewed, open access journal on epigenetics and epigenomics, published quarterly online by MDPI. The Epigenetics Society is affiliated with Epigenomes and its members receive discounts on the article processing charges.

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All Articles (365)

  • Article
  • Open Access

Background/Objectives: Immunotherapy has become a cornerstone in the treatment of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC), but reliable noninvasive biomarkers of prognosis remain limited. We investigated the associations between markers of biological aging and survival outcomes among patients with R/M HNSCC treated with immune checkpoint inhibitors (ICIs). Methods: Peripheral blood samples collected prior to ICI initiation from 100 patients with R/M HNSCC underwent DNA methylation profiling using the Illumina Infinium MethylationEPIC array. Four epigenetic age acceleration measures were estimated from DNA methylation levels and evaluated for associations with progression-free survival (PFS) and overall survival (OS). Results: Greater intrinsic and extrinsic epigenetic age acceleration were each associated with longer PFS (p = 0.025 and p = 0.048, respectively) and OS (p = 0.024 and p = 0.029, respectively). Significant interactions between GrimAge acceleration and chronological age were observed for both PFS (p = 0.010) and OS (p < 0.001). Greater GrimAge acceleration was associated with improved PFS among patients less than 65 years of age but shorter OS among patients 65 years of age or older. Conclusions: In this exploratory study, pretreatment epigenetic aging measures were associated with survival outcomes among patients with R/M HNSCC receiving ICIs. These findings suggest biological aging metrics may have clinical relevance and warrant further investigation as potential noninvasive prognostic biomarkers.

Epigenomes

19 October 2026

Hazard ratios for the associations between the markers of biological aging and progression-free survival (A) and overall survival (B) in R/M HNSCC.
  • Article
  • Open Access

Mikania micrantha, a highly invasive weed, faces constraints on its northward range expansion in South China due to low winter temperatures. Although DNA methylation is increasingly recognized as a mediator of plant stress adaptation, it remains unknown whether epigenetic regulation couples cold-stress tolerance with the production of allelopathic secondary metabolites in invasive plants. Here, we comprehensively characterized genome-wide DNA methylation dynamics and their transcriptional consequences in germinating embryos under three temperature regimes (14 °C, 25 °C, and 30 °C) by integrating whole-genome bisulfite sequencing and RNA-Seq. Exposure to 14 °C significantly delayed germination without arresting the process. Global methylation levels were highest at CG sites (80.21–84.63%), followed by CHG (63.67–66.77%) and CHH (6.63–7.51%) contexts. Integrative analysis identified 1103 differentially methylated region-associated genes, of which 434 were also differentially expressed. Notably, KEGG enrichment of the 434 overlapping genes revealed significant overrepresentation of the sesquiterpenoid and triterpenoid biosynthesis pathways, with key mevalonate (MVA) pathway genes showing altered expression in association with DMRs at 14 °C. Because this is an integrative methylome–transcriptome association study without metabolite quantification or functional validation, these results are consistent with the hypothesis that cold-induced epigenetic reprogramming is associated with transcriptional changes in terpenoid biosynthesis, which may contribute to antioxidant and membrane-protective functions under chilling stress; the possible accumulation of allelopathic sesquiterpene lactones and any role in maintaining competitive advantage during cold seasons remain working hypotheses that require experimental validation. The results of this study offer new epigenetic perspectives and supporting data for the management and prevention of M. micrantha invasion.

Epigenomes

12 October 2026

Seed germination and sample quality assessment of M. micrantha. (a) The workflow chart of M. micrantha seed germination; (b) germ length of germinating M. micrantha seeds; (c) RNA quality analysis of M. micrantha germs; (d) morphology of seedlings cultivated in MS culture medium.
  • Review
  • Open Access

Epigenetic Landscape and Regulation of Secondary Metabolite Accumulation Implicated in Anticancer and Nutraceuticals

  • Deekshitha Kosaraju,
  • Viswanadha Naik Jarapala and
  • Polavarapu Bilhan Kavi Kishor
  • + 5 authors

Plants are important sources for obtaining diverse secondary metabolites which have pharmaceutical importance. Out of multiple factors that modulate their accumulation in vitro and in vivo, epigenetic factors play critical roles, adding an extra layer of regulation. This review focuses on (a) dynamic changes that occur in DNA methylation, histone acetylation, and the role of small RNAs in transcriptional and post-transcriptional modulation that alter secondary metabolism in plants under abiotic stress and (b) the role of epigenetics in secondary metabolite accumulation in the plant cell cultures. Such epigenetic factors are manipulated by applying inhibitors of DNA methylation like 5-azacytidine or histone deacetylation such as trichostatin A in intact plants as well as in cultured plant cells and hairy roots for enhanced production. This article synthesizes current findings on epigenetic engineering for improved synthesis of anticancer compounds and nutraceuticals and lists out limitations and challenges that the pharmaceutical industry is facing for their large scale production and commercialization. Main conclusion: Through epigenetic changes such as DNA methylation, histone acetylation, and non-coding RNAs, plants dynamically fine-tune specific gene expressions to adjust to environmental stresses and mediate secondary metabolite accumulation as a chemical combat mechanism.

Epigenomes

12 October 2026

Stress-induced epigenetic reprogramming regulates secondary metabolite biosynthesis in plants. Environmental stresses, including heat, drought, salinity, cold, UV radiation, and pathogen/herbivore attack, are recognized by plasma membrane-associated receptors, triggering ROS production, MAPK and Ca2+ signaling, and phytohormone-mediated responses (ABA—abscisic acid, JA—jasmonic acid, SA—salicylic acid, ROS—reactive oxygen species, and ethylene). These signaling cascades coordinate in the nucleus to induce epigenetic reprogramming through reduced DNA methylation, active DNA demethylation, histone acetylation, histone methylation, chromatin remodeling, and non-coding RNA (miRNA and lncRNA)-mediated regulation, leading to promoter hypomethylation, chromatin relaxation, and recruitment of RNA polymerase. This leads to secondary metabolite biosynthetic genes, including NES—nerolidol synthase, TPS—terpene synthase, AFS—α-farnesene synthase, and OCS—ocimene synthase, are transcriptionally activated, followed by mRNA export and protein synthesis. The resulting increase in specialized metabolites contributes to improved antioxidant defense, stress tolerance, plant resilience, and the production of high-value natural products with pharmaceutical, nutraceutical, cosmetic, and industrial applications. Note: 1. Red downward arrow beside DNMTs: indicates decreased DNA methyltransferase activity. 2. Red upward arrow beside lncRNA: indicates increased lncRNA expression or activity. 3. Green upward arrows: indicate increased activity of the associated components. 4. Blue upward arrow beside HMTs: indicates increased histone methyltransferase activity and black arrows indicate the direction of signaling or regulatory processes.
  • Review
  • Open Access

Background/Objectives: The aim of this scoping review was to investigate the current role and possible clinical applications of long non-coding RNAs (lncRNAs) in breast cancer diagnosis and treatment. Methods: A thorough search of the PubMed/MEDLINE and Scopus/EMBASE databases was carried out in accordance with the PRISMA-ScR guidelines. The inclusion criteria were as follows: Studies with lncRNA analyses of specimens from breast cancer patients and clinically relevant studies. The exclusion criteria were as follows: in silico and in vitro studies involving animal models; reviews; case series; case reports; comments; editorials; and papers not written in English. The study protocol was registered in the Open Science Framework. Results: After the identification of 1139 records, 312 publications were retrieved and 228 articles were selected for data extraction. Data analysis and the synthesis of evidence showed that lncRNA studies were conducted in breast tumor specimens in 212 studies and in blood samples from breast cancer patients in 20 studies. The most commonly used method was quantitative RT-PCR (in 216 studies), while many studies were complemented by in vitro (n = 177) and animal experiments (n = 75). There were 39 studies that included at least 100 specimens from breast cancer patients. Conclusions: At present, lncRNA analysis is not used in routine clinical practice. Clinically relevant findings coupled by results from in vitro and animal experiments suggest that various lncRNAs after appropriate validation may be used as biomarkers for breast cancer diagnosis and treatment, most notably HSAT164, CCAT2, HOTAIR, and MALAT1. To this end, larger studies involving clinical specimens from clinically relevant subgroups of breast cancer patients will be needed.

Epigenomes

7 October 2026

Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) flowchart.

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Epigenomes - ISSN 2075-4655