Epigenomes最新文献

{"title":"Mutant KRAS Heterogeneity Shapes Nuclear Architecture During Pancreatic Cancer Initiation.","authors":"Gareth Pollin, Angela J Mathison, Elise N Leverence, Thiago Milech De Assuncao, Juan Iovanna, Johnny C Hong, Michael T Zimmermann, Raul Urrutia, Gwen Lomberk","doi":"10.3390/epigenomes10010019","DOIUrl":"10.3390/epigenomes10010019","url":null,"abstract":"<p><strong>Background/objectives: </strong>Pancreatic ductal adenocarcinoma (PDAC) arises predominantly from activating KRAS mutations, yet individual genetic variants differ markedly in signaling output and clinical impact. G12D, the most prevalent variant, strongly drives oncogenic programs, whereas G12R signals less efficiently through the AKT and ERK pathways and is associated with longer patient survival than G12D-driven PDAC.</p><p><strong>Methods: </strong>To elucidate how these differences influence early cellular transformation, we expressed a panel of KRAS mutants in non-cancerous pancreatic ductal epithelial cells as a model of early PDAC initiation and profiled transcriptional and phospho-proteomic responses. We next examined whether epigenetic differences translate into mutation-specific changes in nuclear organization using quantitative imaging of G12D- and G12R-expressing nuclei at 24 and 48 h.</p><p><strong>Results: </strong>Each variant established a unique regulatory program enriched for chromatin remodelers, histone modifiers, and nuclear structural factors, indicating that variant-specific KRAS signaling rapidly develops divergent epigenetic states. Integrated transcriptomic and phospho-proteomic analyses identified G12D and G12R as the most divergent variants. G12D induced pronounced nuclear remodeling, including increased nuclear size, irregular morphology, and reorganization of the nucleolus and spliceosome, consistent with extensive chromatin and transcriptional reprogramming. In contrast, G12R elicited a weaker response, with minimal or delayed structural changes.</p><p><strong>Conclusions: </strong>Together, these findings demonstrate that KRAS mutational context in pancreatic ductal epithelial cells shapes early transcriptional reprogramming that actively remodels nuclear architecture and nuclear sub-compartments. This work establishes nuclear structural remodeling as a structural state of KRAS-driven epigenetic dysregulation during PDAC initiation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Blood DNA CpG Methylation Levels in Response to Methadone Maintenance Treatment: Epigenome-Wide Longitudinal Study.","authors":"Orna Levran, Yuli Kim, Justin Li, Anat Sason, Miriam Adelson, Einat Peles","doi":"10.3390/epigenomes10010018","DOIUrl":"10.3390/epigenomes10010018","url":null,"abstract":"<p><strong>Background/objectives: </strong>Methadone maintenance treatment (MMT) is one of the major pharmacotherapies for opioid use disorder. The underlying mechanisms of addiction and the treatment response are only partially understood. The study's main goal was to identify differential DNA CpG methylation that occurred in response to MMT.</p><p><strong>Methods: </strong>Toward this goal, we have conducted a longitudinal epigenome-wide study of blood samples from 64 patients at the beginning and after 1-3 years of MMT, using a linear mixed model.</p><p><strong>Results: </strong>A total of 1881 differentially methylated probes (DMPs) were identified (FDR < 0.05), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. Among the genes annotated to the top DMPs are <i>DGLUCY</i>, <i>NXNL2</i>, <i>SOX10</i>, and <i>NPAS3</i>. Several genes associated with substance use disorder were annotated by the identified DMPs, including <i>ADORA2A</i>, <i>BDNF</i>, <i>CACNA1D</i>, <i>CREB1</i>, <i>CRHR1</i>, <i>CRY1</i>, <i>DNMT3B</i>, <i>GABRD</i>, <i>GNAS</i>, <i>GRIP1</i>, <i>OXR1</i>, <i>PRKACB</i>, <i>SCN2A</i>, and <i>SCN3A</i>. The most overrepresented pathway is the small GTPase-mediated signal transduction pathway, and the most overrepresented process is the actin cytoskeleton organization.</p><p><strong>Conclusions: </strong>The study provides preliminary insight into the epigenetic effect of MMT. Future studies will have to confirm the DMPs, assess their impact on gene expression, and determine their clinical relevance.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13024794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CpG Methylation of Protein Prenyltransferase Genes <i>FNTA</i>, <i>FNTB</i>, <i>PGGT1B</i> and <i>RABGGTA</i> in Cancer Cell Lines.","authors":"Dominik Jung, Daniel Diehl, Anna Hagemann, Hagen Sjard Bachmann","doi":"10.3390/epigenomes10010017","DOIUrl":"10.3390/epigenomes10010017","url":null,"abstract":"<p><p><b>Background:</b> Protein prenylation is crucial for the function of hundreds of proteins. Aberrant protein prenylation can be caused by the aberrant expression of prenyltransferases (PTases), which has been reported for multiple cancer entities. The reasons for aberrant PTase expression in cancer have not yet been investigated. <b>Methods:</b> We analyzed CpG methylation within promoter-associated CpG islands of the PTase genes <i>FNTA</i>, <i>FNTB</i>, <i>PGGT1B</i>, and <i>RABGGTA</i> via bisulfite conversion and pyrosequencing to assess its role in PTase expression and gain deeper insight into the regulation of protein prenylation in cancer. We used DNA from three benign controls (whole blood samples, peripheral blood mononuclear cells, and HEK293) and 19 human cancer cell lines from various origins to assess DNA methylation within PTase gene promoter-associated CpG islands. For a subset of these cell lines, we measured mRNA expression via qPCR and correlated it with DNA methylation. <b>Results:</b> Methylation across all PTase genes ranged from 1.9 ± 0.9% to 11.4 ± 4.0% (mean methylation ± standard deviation) in benign cells, and 2.3 ± 1.0% to 16.0 ± 5.4% in cancer cells. DNA methylation and mRNA expression of <i>PGGT1B</i> correlated inversely (PCC = -0.75; <i>p</i> = 0.005). <b>Conclusions:</b> We saw no general differences between benign and malignant cells, but observed significant differences between non-malignant controls and multiple individual cancer cell lines regarding the methylation of PTase genes. This was prominently seen in <i>PGGT1B</i> in Caki-1 cells, raising the possibility that DNA methylation is involved in the dysregulation of PTase expression in cancer.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Analysis Reveals Conserved R-Loop Features in Mouse Embryonic Stem Cells.","authors":"Ohbeom Kwon, Hyeonwoo La, Seonho Yoo, Hyeonji Lee, Heeji Lee, Hoseong Lim, Chanhyeok Park, Dong Wook Han, Jeong-Tae Do, Hyuk Song, Youngsok Choi, Kwonho Hong","doi":"10.3390/epigenomes10010016","DOIUrl":"10.3390/epigenomes10010016","url":null,"abstract":"<p><p>R-loops, three-stranded nucleic acid structures formed by an RNA-DNA hybrid, have emerged as important regulators of transcription and genome stability. Although advances in high-throughput sequencing have revealed widespread R-loop landscapes, platform-specific biases hinder the identification of conserved R-loops in specific cell types. Mouse embryonic stem cells, which are transcriptionally active, provide an ideal system for investigating the potential roles of stable R-loops in RNA biology. Here, we integrated 13 independent R-loop profiling datasets from four experimental platforms to define 27,950 Common R-loop regions in mouse embryonic stem cells and characterized their chromatin environment and associated biological functions. Common R-loop regions were reproducibly detected across methods and were preferentially localized to promoter-proximal and genic regions enriched in CpG islands. Genes associated with Common R-loops were highly and stably expressed, showing strong functional enrichment in RNA metabolic processes such as mRNA processing, RNA splicing, and ribonucleoprotein complex biogenesis. Chromatin state analysis revealed that Common R-loops are enriched in transcriptionally active and regulatory contexts. Sequence feature analysis further identified GC skew as a prominent signature of Common R-loops, particularly within transcribed chromatin states. Transcription factor motif analyses have identified distinct regulatory environments in Common R-loop regions, including pluripotency-associated OCT4-SOX2-TCF-NANOG motifs in enhancers, CTCF motifs in open chromatin, and YY1 motifs in promoters. Together, this study provides the first integrated analysis of conserved R-loop regions in mouse embryonic stem cells, revealing their preferential localization at regulatory loci linked to RNA metabolism and highlighting R-loops as structural and functional nodes in RNA biology.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Modifications in the Cell Cycle of <i>C. elegans</i> Embryogenesis: A Comparative Review.","authors":"Anati Alyaa Azhar, Hector Mendoza","doi":"10.3390/epigenomes10010015","DOIUrl":"10.3390/epigenomes10010015","url":null,"abstract":"<p><p>Cell division is a highly regulated process that actively involves dynamic changes to the genetic material within the nucleus. DNA is faithfully replicated in the S-Phase of the cell cycle, being converted from loose, relaxed chromatin into tight, condensed chromosomes to be segregated in mitosis. In addition to scaffolding proteins that shape these mitotic chromosomes, post-translational modifications of histones within nucleosomes modulate chromosome dynamics throughout the cell cycle. In this review, we use a comparative approach to highlight some of the major epigenetic marks affected by the cell cycle during embryogenesis of <i>Caenorhabditis elegans</i>: H4K20me1, H3S10ph, H4S1ph, H2AS1ph, and H3T118ph. These five histone post-translational modifications will be specifically highlighted in the context of the mitotic cell cycle, as they are well documented in the <i>C. elegans</i> literature.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Activity of Cancer Therapy Drugs Revealed by HeLa TI Cell-Based Assay.","authors":"Varvara Maksimova, Valeriia Popova, Alyona Kholodova, Julia Makus, Olga Usalka, Eugenia Lylova, Aleksandr Kudriashov, Gennady Belitsky, Marianna Yakubovskaya, Kirill Kirsanov","doi":"10.3390/epigenomes10010014","DOIUrl":"10.3390/epigenomes10010014","url":null,"abstract":"<p><strong>Background/objectives: </strong>The aberrant epigenetic landscape of cancer cells has attracted wide attention, motivating the search for new epigenetically active drugs both for anticancer therapy and for overcoming the drug resistance promoted by epigenetic changes. The use of epi-drugs in cancer therapy requires consideration of the influence of applied treatment on epigenetic regulation of gene expression. Therefore, it is reasonable to screen epigenetically active compounds among the drugs widely used in clinical oncology.</p><p><strong>Methods: </strong>We applied the HeLa TI cell-based assay to analyze the epigenetic activity of 40 drugs including 22 chemotherapeutic, 2 immunotherapeutic, 13 targeted, and 3 palliative agents. Reactivation of the epigenetically silenced <i>GFP</i> reporter gene integrated into the genome of HeLa TI cells was assessed using flow cytometry.</p><p><strong>Results: </strong>Statistically significant increases in the proportions of GFP-positive cells were demonstrated for the alkylating agent chlorambucil; the antimetabolites cytarabine, fluorouracil, gemcitabine, and pemetrexed; the platinum-based compounds cisplatin, and oxaliplatin; the topoisomerase inhibitor topotecan; and the antimicrotubule agents docetaxel, vincristine, and eribulin. Epigenetic activity was also detected for the targeted-therapy agents AZD8055, wortmannin, and cetuximab, as well as for the corticosteroid dexamethasone. Thus, epigenetic activity was revealed for 15 drugs widely used in cancer therapy, which possess different modes of action.</p><p><strong>Conclusions: </strong>Our findings show that many anticancer therapy agents modulate the epigenetic landscape of cancer cells, providing a rationale for expanding their therapeutic applications and enhancing the efficacy of combination strategies by overcoming epigenetically driven chemoresistance.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Epigenetic Battleground: Host Chromatin at the Core of Infection.","authors":"Fabrício Castro Machado, Nilmar Silvio Moretti","doi":"10.3390/epigenomes10010013","DOIUrl":"10.3390/epigenomes10010013","url":null,"abstract":"<p><p>Chromatin dynamics are usually modulated by histone epigenetic post-translational modifications, which rapidly and reversibly govern accessibility and transcriptional responsiveness. During microbial infection, this regulatory layer becomes a highly contested interface where host defense mechanisms and pathogen-driven subversion strategies converge and compete. Many infectious agents exploit chromatin to reprogram gene expression, creating cellular environments that are conducive to infection, proliferation, and persistence. Diverse strategies have been described for viruses, bacteria, fungi, protozoa and nematodes, including the direct secretion of acetyltransferases and methyltransferases, interference with host chromatin-binding proteins, subcellular localization of transcriptional factors or epigenetic regulators, and metabolic availability manipulation. Concurrently, host cells activate immune and stress-response genes to mount rapid, adaptable antimicrobial responses. Recent advances in genome-wide, single-cell, and spatial omics profiling have begun to reveal the temporal and cell-type-specific dynamics of the host genome at the core of infection. This review synthesizes current insights into how chromatin is rewired by the major categories of pathogens during infection, highlighting representative case studies across infective agents and the functional consequences for immunity and cell fate. In addition, we discuss emerging techniques for epigenomic and transcriptomic data collection, and the potential of targeted host-directed therapeutic strategies. Chromatin regulation is thus a promising field of study and a possible target for next-generation interventions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12937675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary Evidence of Blood DNA Methylation Changes in Pregnant Women Adhering to a Mediterranean Diet.","authors":"Grace Tavelli, Nikki Schultz, Joanna Brisbane, Nina Kresoje, Samantha Lodge, Jeremy K Nicholson, Nicola J Armstrong, Desiree Silva, Nina D'Vaz, David Martino","doi":"10.3390/epigenomes10010012","DOIUrl":"10.3390/epigenomes10010012","url":null,"abstract":"<p><strong>Background/objectives: </strong>Consumption of a Mediterranean diet (MD) has been associated with reduced incidence of non-communicable diseases and reduced overall mortality, with epigenomic effects representing plausible mediators. The aim of this pilot study was to explore potential epigenetic associations between DNA methylation markers in blood and adherence to an MD in pregnancy.</p><p><strong>Methods: </strong>Fifty-two pregnant women with high or low adherence to an MD throughout pregnancy, who participated in the BioMood ORIGINS study, were selected using an extremes-of-exposure design. DNA methylation (DNAm) profiles from whole blood were generated using the TWIST human methylome panel. We conducted both genome-wide and candidate gene-based differential methylation analyses to identify epigenetic variations between the study groups. Furthermore, we explored potential associations between blood methylation patterns and circulating inflammatory markers (GlycA, GlycB and SPC) previously observed to exhibit differential abundance in the same cohort of women.</p><p><strong>Results: </strong>There were no genome-wide significant differences in methylated dinucleotides between MD groups (<i>p</i>-value < 5 × 10^-8); however, a region-based analysis identified 2210 differentially methylated regions (DMRs) (FDR < 0.05, absolute maximum logFC > 1) annotated to 1537 genes, significantly enriched in metabolic, inflammatory and neuronal signaling pathways. Leveraging publicly available data, we replicated nine novel DMR associations. Changes in circulating phospholipid inflammatory markers were significantly associated with a small methylation difference in Lipin-1 (<i>LPIN1)</i>, albeit with a small effect size (<i>p</i>-value < 5 × 10^-8). A look-up analysis of previously reported MD-associated genes in this cohort detected small but statistically significantly different methylation of CpGs located within collagen type XVIII alpha 1 (<i>COL18A1)</i> and peroxisome proliferator-activated receptor gamma, coactivator 1 beta (<i>PPARGC1B)</i> gene regions.</p><p><strong>Conclusions: </strong>We provide preliminary evidence for modest methylation changes in specific genes associated with adherence to an MD.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of HERV-K (HML2) Expression in Colorectal Cancer Samples.","authors":"Valentina S Obrezanenko, Polina M Shulga, Anastasia G Volkova, Anastasia A Primova, Yulia A Remizova, Ivan O Meshkov, Alexandra D Kikot, Daria A Tarasova, Ekaterina S Bolashova, Alexey A Ivashechkin, Antonida V Makhotenko, Ekaterina A Snigir, Yulia A Masyukova, Elizaveta I Radion, Olesya A Kuznetsova, Maria S Cheporova, Michail Y Fedyanin, Alexey A Tryakin, Valentin V Makarov, Vladimir S Yudin, Anton A Keskinov, Anna S Makarova","doi":"10.3390/epigenomes10010011","DOIUrl":"10.3390/epigenomes10010011","url":null,"abstract":"<p><strong>Background: </strong>HML-2 subgroup mobile genetic elements of the HERV-K family were described to participate in carcinogenesis processes, but their expression and epigenetic regulation in molecular subtypes of colorectal cancer (CRC) remain partly characterized. The present study aimed to evaluate the expression of HML-2 elements using RNA-sequencing data in paired tumor and normal intestinal tissue samples from 63 patients with CRC to identify patterns of the retrotransposons' activity in different molecular subtypes (CMSs).</p><p><strong>Methods: </strong>RNA-sequencing and DNA methylation data were analyzed for paired CRC and normal tissue samples. HERV-K expression was assessed using three bioinformatics tools: Telescope (version 1.0.3), TEtranscripts (version 2.2.3), GeneTEFlow (version 2020). Molecular tumor subtypes were defined using the CMScaller (version 0.99.2) program. The results of the HML-2 loci expression analysis were supplemented with the HML-2 proteins expression data obtained by quantitative RT-PCR.</p><p><strong>Results: </strong>HML-2 expression assessment by GeneTEFlow (version 2020), TECount (version 2.2.3) and Telescope (version 1.0.3) showed high convergence: the Pearson correlation coefficient for each tool exceeded 0.88. Several HML-2 loci were identified as differentially expressed in CRC samples of different CMS. The PCR results confirmed an increase in HML-2 expression in tumor tissues. For all CMSs, an inverse association was detected between differential methylation of CpG sites and differential expression of HML-2 loci. Associations of HML-2 expressions with differentially expressed genes in which they are located were found, and for a number of such genes an inverse relationship between the expression level and the methylation level of their promoters were demonstrated, and data on the involvement in the pathogenesis of CRC were described: <i>CR1</i>, <i>CD48</i>, <i>TTLL3</i>, <i>ABCC2</i> and <i>ZNF420</i>. Expression signatures associated with the activity of the RIG-I-like receptor signaling cascade were identified in CMS1-3 CRC samples, which may indicate the possible implementation of viral mimicry against the background of HML-2 activation.</p><p><strong>Conclusions: </strong>Analysis of the expression of HML-2 and its association with CpG methylation contributes to a comprehensive interpretation of the CRC pathogenesis mechanisms.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12922068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146260385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic-Epigenetic Interplay in Epilepsy: Pathways, Biomarkers, and Epigenome-Targeted Therapies.","authors":"Andra-Giorgiana Zaruha, Patricia Codreanu, Mădălin-Codruț Coman, Monica Andreea Novac Ii, Simona Gabriela Duță-Ion, Ioana Ruxandra Jugănaru, Iulian Andrei Hotinceanu, Andra Dan, Livia Mălina Burtavel, Anca-Elena Eftenoiu, Diana Bârcă, Andreea Ionescu, Cerasela Paraschiv, Viorica-Elena Rădoi","doi":"10.3390/epigenomes10010010","DOIUrl":"10.3390/epigenomes10010010","url":null,"abstract":"<p><p>Epilepsy is a heterogeneous neurological disorder with a strong genetic basis, yet recent evidence underscores the critical role of epigenetic mechanisms in its pathogenesis. This review synthesizes current knowledge on how chromatin remodeling, histone modifications, DNA methylation, and transcriptional regulation intersect with classical channelopathies and signaling pathways. We emphasize how epigenetic dysregulation contributes to neuronal excitability and network plasticity, particularly through interactions with mTOR, PI3K-AKT, and GABAergic signaling cascades. The convergence of genetic mutations and epigenetic modifications creates a dynamic landscape in which environmental factors can modify gene expression and contribute to the development of epilepsy. Emerging therapeutic strategies-including epigenetic drugs (HDAC inhibitors, DNMT inhibitors), CRISPR/dCas9-based epigenome editing, and multi-omics approaches-offer promising avenues for precision medicine. This review provides a comprehensive synthesis of genetic and epigenetic mechanisms in epilepsy, examining how these layers interact to produce disease phenotypes and discussing the therapeutic implications of this multilayered regulation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}