Epigenomes最新文献

{"title":"Age-Related Epigenetic Drift Shapes Coordinated microRNA Promoter Methylation and Expression in Prostate Cancer.","authors":"Fernando Bergez-Hernández, Martín Irigoyen-Arredondo, Lizeth Carolina Flores-Méndez, Alejandra Paola Martínez-Camberos","doi":"10.3390/epigenomes10020027","DOIUrl":"https://doi.org/10.3390/epigenomes10020027","url":null,"abstract":"<p><p><b>Background:</b> Aging is the strongest risk factor for prostate cancer (PCa). It is accompanied by progressive epigenomic divergence, known as epigenetic drift, particularly affecting DNA methylation at regulatory regions. However, the extent to which age-associated promoter methylation contributes to coordinated microRNA (miRNA) expression changes in PCa remains incompletely characterized. <b>Methods:</b> We conducted an integrative in silico analysis of 449 primary tumors from the TCGA-PRAD cohort. Age was modeled as a continuous variable. Age-related miRNA expression changes were estimated from miRNA-seq data using DESeq2. Promoter DNA methylation changes (±2 kb from transcription start sites) were assessed using Illumina 450K arrays and linear regression. MiRNAs showing significant age-associated alterations at both expression and methylation levels were classified as concordant or discordant based on directionality and prioritized using an effect size-based concordance score. We analyzed experimentally validated targets of prioritized miRNAs through functional enrichment and network-based approaches to identify convergent regulatory pathways. <b>Results:</b> Initially, we identified 105 age-associated miRNAs. After filtering, 65 candidates remained. Of these, we found 37 miRNAs with significant age-associated changes at both layers, including 20 concordant and 17 discordant miRNAs. These comprised well-characterized cancer-associated miRNAs and lesser-studied candidates enriched in CpG-rich regulatory regions. Network analyses revealed a limited set of genes under convergent regulation by multiple age-associated miRNAs. These implicated pathways are related to cell cycle control, apoptosis, stress response, and epigenetic regulation. <b>Conclusions:</b> Our findings support a model in which age-dependent promoter methylation drift contributes to coordinated miRNA deregulation in PCa. This convergence highlights biologically plausible miRNA biomarkers and age-sensitive epigenetic circuits relevant to prostate carcinogenesis.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790339","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":"Novel Perspectives on <i>ATP8A2</i> Regulation: Evidence for Parental Imprinting and Chimeric Transcript Formation.","authors":"Abdelhamid Bouramtane, Badreddine Elmakhzen, Amal Ouskri, Mohamed Ahakoud, Laila Bouguenouch, Karim Ouldim, Omar Askander","doi":"10.3390/epigenomes10020026","DOIUrl":"https://doi.org/10.3390/epigenomes10020026","url":null,"abstract":"<p><p><b>Background</b>: Parental imprinting plays a crucial role in epigenetic regulation and is increasingly recognized for its involvement in neurodevelopmental disorders. Although <i>ATP8A2</i> is considered a non-imprinted gene; However, the marked phenotypic variability observed across related disorders suggests that additional regulatory layers may influence its expression. <b>Methods</b>: We investigated the imprinting-like status of <i>ATP8A2</i> through functional analyses of a splicing variant (c.1580-3C>G) identified in a patient diagnosed with Cerebellar Ataxia, Mental Retardation, and Disequilibrium syndrome type 4 (CAMRQ4). Sanger sequencing was used to assess allelic expression and identify aberrant transcripts. <b>Results</b>: Our analyses revealed an allelic expression imbalance suggestive of parental imprinting of <i>ATP8A2</i>. Moreover, Sanger sequencing led to the identification of a novel <i>ATP8A2</i>-<i>RAB3GAP2</i> chimeric transcript, pointing to a previously unreported transcriptional event, the functional relevance of which remains to be determined. <b>Conclusions</b>: These findings indicate that <i>ATP8A2</i> may be subject to imprinting-like regulation and involved in atypical splicing events with unknown significance. This highlights the need for further investigation into the epigenetic and transcriptional complexity of <i>ATP8A2</i>-related neurodevelopmental disorders.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790256","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":"Mitochondrial D-Loop Region Methylation Is Not Altered in Children with Autism Spectrum Disorder.","authors":"Andrea Stoccoro, Carmela Serpe, Antonia Parmeggiani, Vincenzo Davide Catania, Mario Lima, Alessandro Ghezzo, Cristina Panisi, Marida Angotti, Beatrice Pranzetti, Provvidenza Maria Abruzzo, Cinzia Zucchini, Lucia Migliore, Marina Marini, Fabio Coppedè","doi":"10.3390/epigenomes10020025","DOIUrl":"https://doi.org/10.3390/epigenomes10020025","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Although the etiopathogenesis of autism spectrum disorder (ASD) remains incompletely elucidated, current evidence supports a multifactorial model involving genetic and environmental factors that interact to induce a heterogeneous range of symptoms. In recent years, epigenetic mechanisms, particularly DNA methylation, have been recognized as key contributors to ASD pathophysiology. Alterations in mitochondrial DNA (mtDNA) methylation are also emerging as relevant contributors in several human conditions. The mitochondrial D-loop, a non-coding control region essential for mtDNA replication and transcription, is considered a hotspot for epigenetic regulation and its methylation levels have been found altered in various diseases, such as cancer, metabolic disorders, and neurological illness. However, to date, no studies have investigated mtDNA methylation changes in ASD. <b>Methods</b>: We analyzed the average methylation levels of a fragment containing ten CpG sites within the D-loop region and the mtDNA copy number in peripheral blood samples from 49 children with ASD and 50 neurotypically developing (NT) controls using Methylation-Sensitive High-Resolution Melting and quantitative PCR. <b>Results</b>: No significant differences in D-loop methylation levels were observed between ASD and NT children. Similarly, the mtDNA copy number did not differ between the two groups. No significant correlations were found between D-loop methylation or mtDNA copy number and either ASD severity or age. <b>Conclusions</b>: This is the first study investigating mtDNA methylation in ASD. Our results indicate that methylation of the D-loop region and the mtDNA copy number are not altered in ASD children. Further studies including larger cohorts and extended mtDNA regions are warranted to confirm and expand these findings.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790329","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 Many Faces of SetDB1.","authors":"Stanislav E Romanov, Dmitry E Koryakov","doi":"10.3390/epigenomes10020024","DOIUrl":"https://doi.org/10.3390/epigenomes10020024","url":null,"abstract":"<p><p>The conserved protein SetDB1 has been identified in various vertebrate and invertebrate groups. It plays key roles in vital processes such as germline and nervous system development, immune response, tumorigenesis, cell cycle progression, and others. SetDB1 is initially characterized as an enzyme that methylates lysine 9 on histone H3, leading to gene silencing, which is traditionally considered its primary function. However, SetDB1 also targets about a dozen nuclear, cytoplasmic, and membrane proteins as substrates. Moreover, some functions of SetDB1 do not require methyltransferase activity. Due to its SUMO-interacting motif, Tudor domain, and methyl-binding domains, SetDB1 interacts with a wide range of complexes that regulate protein stability and activity, signal transduction pathways, and chromatin spatial organization. In this review, we aim to expand the classical view of SetDB1 as solely a histone methyltransferase and to highlight the broader diversity of its functions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790266","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":"Natural Compounds as Epimodulators in Epithelial Ovarian Cancer.","authors":"Mélida Del Rosario Lizarazo-Taborda, Julio César Villegas-Pineda, Holver Parada, Fabian Galvis, Javier Soto","doi":"10.3390/epigenomes10020023","DOIUrl":"https://doi.org/10.3390/epigenomes10020023","url":null,"abstract":"<p><p>Epithelial ovarian carcinoma (EOC) is the most common type of ovarian cancer and represents the most lethal gynecologic neoplasm. EOC is usually diagnosed at late stages due to its nonspecific signs and symptoms. Although significant clinical advances have been made in other types of malignancies, EOC remains a disease that requires further biological research to identify new therapeutic targets or new treatment alternatives, as conventional approaches are often ineffective or lead to the development of resistance and unwanted side effects. There are a significant number of natural products from which commercially available drugs have been derived, largely for the treatment of cancer, but none of them focus on epigenetic changes in specific targets in EOC. Based on the above, this work focuses on describing the in vitro and in vivo findings from the last twelve years derived from the action of important phytochemicals on epigenetic targets in ovarian cancer, among other mechanisms of action, revealing that there is a significant gap to be bridged in terms of the transition from basic to applied research regarding the potential of plant-derived molecules as possible epidrugs in EOC.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790346","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 Age Feedback as a Catalyst for Sustained Lifestyle Change: One-Year Results from the EU iHelp Study.","authors":"Nien-Yu Yang, Yicong Huang, Chaewon Park, Te-Min Ke, Graham Tilston, George Manias, Dimosthenis Kyriazis, Jon Young, Susan Hart, Graham Fulford, Artitaya Lophatananon, Kenneth R Muir","doi":"10.3390/epigenomes10020022","DOIUrl":"https://doi.org/10.3390/epigenomes10020022","url":null,"abstract":"<p><strong>Background: </strong>Sustaining long-term lifestyle change remains a major challenge in preventive health. Epigenetic clocks offer a dynamic, modifiable measure of biological ageing that may enhance motivation when returned to individuals.</p><p><strong>Objectives: </strong>This study had two aims: (1) to evaluate whether personalised health reports integrating epigenetic age, polygenic cancer risk scores, and lifestyle metrics could motivate sustained behavioural change; and (2) to examine variability across epigenetic clock generations to inform the selection of a suitable model for participant feedback.</p><p><strong>Methods: </strong>A total of 178 adults were recruited via the Graham Fulford Charitable Trust community testing programme, and 91 completed a one-year follow-up survey assessing behavioural, psychological, and knowledge-related outcomes. DNA methylation data from 140 samples were used to compare 14 epigenetic clocks across four generations.</p><p><strong>Results: </strong>Most participants reported positive lifestyle changes, including feeling healthier (72.5%), increased physical activity (60.4%), and improved diet (47.3%). Gains were also observed in health knowledge (63.7%) and psychological well-being (31.9%). Epigenetic clock comparisons revealed substantial heterogeneity across models. Zhang2019-BLUP was selected as a stable and interpretable measure of biological age that can be readily communicated to participants, supporting empowerment and improved health literacy, rather than serving only as a risk prediction metric.</p><p><strong>Conclusions: </strong>Personalised biomarker feedback including epigenetic age combined with lifestyle and wearable data can support self-reported improvements in health-related behaviours. Community-based delivery through trusted local networks proved effective. The marked variation between epigenetic clocks highlights the importance of selecting models designed for clear communication when used in public-facing health interventions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147790296","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":"MicroRNA Regulation in Kidney Interstitial Fibrosis.","authors":"Hirofumi Sakuma, Satoshi Kawaguchi, Yuya Kobayashi, Akiko Koizumi, Naoki Nakagawa","doi":"10.3390/epigenomes10010021","DOIUrl":"10.3390/epigenomes10010021","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are small non-coding RNAs that play central roles in post-transcriptional gene regulation and cellular homeostasis maintenance. Dysregulation of miRNA expression is increasingly recognized as a key contributor to tissue injury during the acute phase and to disease progression in the chronic phase. Chronic kidney disease (CKD) commonly progresses and ultimately leads to kidney failure through interstitial fibrosis, which is the final common pathway of CKD progression. Interstitial fibrosis is driven not only by fibroblast activation but also by phenotypic transitions in injured tubular epithelial cells, infiltrating macrophages, and peritubular capillary cells. These multifaceted cellular pathways induce and exacerbate interstitial fibrosis, and several miRNAs have been identified as important regulators of these pathways. In addition to fibrotic pathophysiological features, disease-specific dysregulation of miRNAs has been increasingly detected in various causes of CKD, including diabetic kidney disease, chronic glomerulonephritis, and nephrosclerosis. In this review, we provide an integrated overview of miRNA-mediated regulation in CKD, with particular emphasis on cell lineage functions within fibrotic pathways and disease-specific roles. Finally, we discuss the emerging potential of miRNAs as biomarkers and therapeutic targets for CKD and highlight future research directions.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534427","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":"Epigenetics of Genes Displaying High and Preferential Expression in Myoblasts.","authors":"Kenneth C Ehrlich, Michelle Lacey, Sriharsa Pradhan, Melanie Ehrlich","doi":"10.3390/epigenomes10010020","DOIUrl":"10.3390/epigenomes10010020","url":null,"abstract":"<p><strong>Background/objectives: </strong>Genome-wide studies of differential DNA methylation often focus on its role in turning transcription on or off. Here we report some atypical epigenetic/transcription relationships for 92 genes that are highly and preferentially expressed in primary human myoblasts relative to heterologous cell cultures.</p><p><strong>Methods: </strong>We compared methylomes and myoblast-specific differentially methylated regions (DMRs) with methylomes, chromatin profiles, and transcriptomes for many different cell populations.</p><p><strong>Results: </strong>We found that myoblast-associated promoter hypomethylation was unusually prevalent among the 92 myoblast-preferential genes. Sometimes this promoter hypomethylation was seen as a myoblast-associated extension of their constitutively unmethylated region at a CpG island. All 92 genes showed some myoblast-specific hypomethylation, including 32 genes at tissue-specific super-enhancers or broad H3K4-trimethylated promoters. Myoblast hypermethylated DMRs were also associated with almost half of the myoblast-preferential genes. These hypermethylated DMRs were often in intragenic locations embedded in H3K36-trimethylated chromatin in myoblasts.</p><p><strong>Conclusions: </strong>Our analysis suggests that some of the hypermethylated DMRs repress cryptic, alternative, or adjacent promoters. Myoblast hypermethylated DMRs may also downmodulate expression in myoblasts to avoid yet higher RNA levels found in adult or fetal skeletal muscle tissue. The epigenetic insights that were obtained can help elucidate the transcription regulation of some of these genes (e.g., <i>MUSK</i>, <i>RAPSN</i>, <i>HEYL</i>, <i>SYNPO2</i>, <i>SYNPO2L</i>, <i>STAC3</i>, <i>PITX2</i>, and <i>TPPP3</i>) that are implicated in congenital myasthenic syndromes, myasthenia gravis, muscle repair, heart dysfunction, or cancer. This study supports cell type-specific roles for DNA hypo- and hypermethylation as a modulator of transcription levels, in addition to being an on-off switch during differentiation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13025873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534377","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":"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":3.5,"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":3.5,"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}