Epigenomes最新文献

{"title":"5mC and 6mA DNA Methylation in the Fungal Kingdom: From Genome Defense to Epigenetic Regulation.","authors":"Daniil P Malyshev, Vasiliy V Belov, Elizaveta S Gromova, Andrey A Eremin, Maria I Zvereva, Alexander V Sergeev","doi":"10.3390/epigenomes10020037","DOIUrl":"10.3390/epigenomes10020037","url":null,"abstract":"<p><p>DNA methylation, the covalent addition of methyl groups to cytosine (5mC) or adenine (6mA) in DNA, is a fundamental mechanism of epigenetic inheritance conserved from bacteria to humans. Fungi provide a uniquely informative window into the evolutionary logic of methylation systems. Spanning more than 1 billion years of diversification, the kingdom encompasses species that have lost cytosine methylation entirely, lineages that use 5mC to silence transposons and drive the irreversible genome-defense process known as repeat-induced point mutation (RIP), and early-diverging lineages, in which 6mA has emerged as a prominent chromatin mark. The methyltransferases underlying these strategies (DIM-2, RID, DNMT1-RFD, DNMT5, and the MT-A70 complex) and the recently characterized demethylases Dmt1 and CcTet are structurally and mechanistically distinct from their mammalian counterparts. Here we review the mechanisms, targets, and biological functions of fungal DNA methyltransferases and demethylases, incorporating cryo-EM structural insights into DIM-2 and DNMT5 catalysis, analyses of DNMT gene loss as a continuous evolutionary process, the antiviral role of DIM-2 in vegetative hyphae, and the emerging model of 6mA as a heritable regulatory mark in early-diverging lineages. By integrating these advances, this review offers the updated and comprehensive account of DNA methylation across fungi.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13297926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320711","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":"Dual Functionality of miRNAs During HIV Infection: From Viral Genome Suppression to Immune Response Modulation.","authors":"Anna M Timofeeva, Kseniya S Aulova, Georgy A Nevinsky","doi":"10.3390/epigenomes10020039","DOIUrl":"10.3390/epigenomes10020039","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background/objectives: &lt;/strong&gt;As important post-transcriptional and epigenetic regulators of gene expression, miRNAs play a pivotal role in modulating host-virus interactions. While prior reviews have addressed either direct miRNA-HIV genome interactions or miRNA-mediated immune modulation in isolation, the integrated dual functionality of these molecules has not been systematically characterized. This review aimed to comprehensively explore how miRNAs that target the HIV-1 genome simultaneously modulate key innate and adaptive host immune signaling pathways. The conceptual novelty of this study is determined not by the identification of previously unknown miRNA-target gene pairs, but by the systemic integration of two regulatory levels (direct inhibition of the viral genome and modulation of the host cell immune signaling pathways) within a unified analytical framework. Such an integrated approach reveals a proviral regulatory network that remains non-obvious when each of these levels is examined separately.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A narrative review was conducted using PubMed, Scopus, Web of Science, and Google Scholar (all years through 2025). In Stage 1, publications reporting experimentally confirmed interactions between host miRNAs and the HIV-1 genome were identified, yielding a curated set of 15 miRNAs. In Stage 2, target genes for each miRNA were retrieved from miRTarBase, TarBase (experimentally validated) and TargetScan 8.0 (in silico predicted). In Stage 3, target genes were manually mapped to key immune signaling pathways (TLR, NF-κB, JAK-STAT). In Stage 4, targeted literature searches were performed for each miRNA-target gene pair to identify direct experimental evidence of interaction. All stages were performed by two independent researchers, with discrepancies resolved by a third.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Fifteen host miRNAs with experimentally confirmed binding to the HIV-1 genome were identified, targeting viral genes including &lt;i&gt;nef&lt;/i&gt;, &lt;i&gt;pol&lt;/i&gt;, &lt;i&gt;vpr&lt;/i&gt;, &lt;i&gt;gag&lt;/i&gt;, &lt;i&gt;env&lt;/i&gt;, &lt;i&gt;vif&lt;/i&gt;, and the 3'-UTR. Thirteen of these miRNAs were found to regulate components of major immune pathways. miR-92a-3p, miR-29a/b-3p, miR-150-5p, and miR-125b-5p emerged as the most pleiotropic regulators, simultaneously suppressing TLR signaling (TLR3, TLR7, TLR8, MyD88, TRAF3/6, IRAK1/4), NF-κB components (REL, RELA, NFKB1), JAK-STAT effectors (STAT1-3, STAT5A/B, JAK2), and negative regulators of cytokine signaling (SOCS and PIAS family proteins). miR-133b and miR-196b-5p were found to selectively regulate SOCS/PIAS proteins without involvement in other analyzed pathways, suggesting potential for selective therapeutic targeting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The analyzed miRNAs exhibit functional dualism, acting as direct post-transcriptional suppressors of the HIV-1 genome while simultaneously functioning as epigenetic modulators of host immune signaling. These two modes of action are not independent but ","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320761","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":"Nuclear Transfer Perturbs Genomic Balance.","authors":"Eryk Andreas, Justin C St John","doi":"10.3390/epigenomes10020038","DOIUrl":"10.3390/epigenomes10020038","url":null,"abstract":"<p><strong>Background: </strong>The transfer of a nucleus from one oocyte to another offers patients harbouring high levels of mitochondrial DNA mutation and sufferers of frequent fertilisation failure or early embryonic arrest the potential to have healthy children. However, a small amount of mtDNA is carried over with the nucleus as the transfer takes place. Consequently, we still need to distinguish between the effects of the carryover and the transfer of a nucleus itself from a mature oocyte.</p><p><strong>Methods: </strong>To overcome this, we analysed a series of hatching stage blastocysts generated using metaphase II spindle transfer and mitochondrial supplementation. The latter approach also introduces a small amount of mtDNA into the oocyte as fertilisation takes place. For both manipulations, an autologous approach was used to overcome the effects of third-party transfer.</p><p><strong>Results: </strong>We then compared the changes in global gene expression between the two groups. We found that the nuclear transfer process affected a number of gene networks and pathways. These included metabolic, cell cycle, inflammatory and immune, and epigenetic responses. A comparison with earlier stage blastocysts did not suggest that the cause was due to developmental delay.</p><p><strong>Conclusions: </strong>Critically, these changes could affect offspring health and well-being as is the case following somatic cell nuclear transfer.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320763","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":"Low Depth Epigenetic Mapping of Maturation Versus Retrodifferentiation in HepaRG Cells.","authors":"Hector Hernandez-Vargas, Kilian Petitjean, Marie-Pierre Lambert, Yoann Daniel, Isabelle Chemin, Anne Corlu, Chloe Goldsmith","doi":"10.3390/epigenomes10020036","DOIUrl":"10.3390/epigenomes10020036","url":null,"abstract":"<p><p><b>Background:</b> Long-read, single-CpG-resolution sequencing is redefining the information-to-depth ratio in epigenomics. While conventional methylome analysis often requires high coverage, we propose a scalable pipeline designed to extract high-density regulatory logic from shallow sequencing data. <b>Methods:</b> By utilizing the progenitor-like HepaRG cell line as a model for liver plasticity, we validated this framework across two divergent developmental trajectories: hepatic maturation and sphere-induced retrodifferentiation. Our technical approach combines CpG-centric enrichment and regional methylation aggregation to reconstruct regulatory landscapes from sparse data. Using long-read Nanopore sequencing, we mapped the dynamics of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). <b>Results:</b> Our pipeline revealed that these trajectories are not inverse processes but engage distinct epigenetic strategies. Hepatic maturation is characterized by the accumulation of 5hmC that partially targets repressive heterochromatin (H3K9me3, H4K20me3) and pioneer factors such as FOXA2. In contrast, retrodifferentiation increases 5mC, potentially silencing adult regulators such as HNF1A via Polycomb-associated networks. In addition, aggregation-based analysis can distinguish widespread focal perturbations from a restricted subset of transcription factors that translate epigenetic changes into regional accessibility. <b>Conclusions:</b> This study provides a scalable computational framework for investigating cellular fate transitions, proving that high-value epigenetic insights are attainable even at reduced sequencing depths.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320743","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":"Longitudinal Analysis of Peripheral MicroRNA Expression and Depressive Symptom Severity Change in a Community Cohort.","authors":"Jan Dahrendorff, Chengqi Wang, Agaz Wani, Zachary Graham, Allison E Aiello, Annie Qu, Derek E Wildman, Monica Uddin","doi":"10.3390/epigenomes10020035","DOIUrl":"10.3390/epigenomes10020035","url":null,"abstract":"<p><strong>Background: </strong>Depression is a heterogeneous and recurrent condition, whose underlying biological mechanisms remain poorly understood. MicroRNAs (miRNAs), small non-coding RNAs that regulate post-transcriptional gene expression, are increasingly implicated in cross sectional miRNA studies of depression and depressive symptoms; however, longitudinal studies capturing miRNA changes over time in relation to depression are scarce.</p><p><strong>Methods: </strong>We conducted small RNA sequencing of leukocyte-derived miRNAs at two timepoints in a prospective community-based cohort (<i>n</i> = 185) to assess associations between within-person changes in depressive symptom severity (ΔPHQ-9) and longitudinal miRNA expression. Differential expression analyses were performed using a paired limma-voom framework, adjusting for covariates (baseline PHQ-9, sex, age, DNAm-derived immune cell covariates and ancestry components derived from matched blood samples) and within-subject correlation.</p><p><strong>Results: </strong>Although no miRNAs survived multiple-testing correction, 68 mature unique miRNAs showed nominal associations (<i>p</i> < 0.05) with depressive symptom severity change (ΔPHQ-9). Several top candidates, including miR-493-3p, miR-409-3p, and miR-323a-3p, displayed expression patterns aligning with prior reports implicating these miRNAs in stress responsivity, synaptic plasticity, and neurodevelopmental regulation. Exploratory follow-up of predicted targets of the nominally symptom-associated miRNAs converged on genes in pathways central to depression biology, including neurotransmission, HPA axis/inflammatory signaling, neuroplasticity, and circadian regulation. Enrichment analyses highlighted receptor tyrosine kinase and intracellular signaling cascades, hypothalamic-pituitary-adrenal axis feedback, and inflammatory pathways.</p><p><strong>Conclusions: </strong>These findings provide preliminary evidence that peripheral miRNA expression changes may reflect depressive symptom trajectories, highlighting potential molecular pathways involved in depression. Further studies with larger samples and broader symptom severity are warranted to validate these dynamic miRNA signatures.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320709","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":"<i>LincRNA-BC7</i> as a Modulator of Olaparib Sensitivity in Triple-Negative Breast Cancer.","authors":"Olalekan Olatunde Fadebi, Babatunde Adebola Alabi, Richard Khanyile, Zodwa Dlamini, Rahaba Marima","doi":"10.3390/epigenomes10020034","DOIUrl":"10.3390/epigenomes10020034","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) remains a clinical challenge due to its aggressive nature and the frequent emergence of therapeutic resistance. While the role of protein-coding genes in DNA repair is well-documented, the regulatory contributions of the non-coding genome, specifically long intergenic non-coding RNAs (lincRNAs), remain largely undefined.</p><p><strong>Objectives: </strong>In this study, we characterize the biological significance of <i>LincRNA-BC7</i>, a novel transcript identified within the breast cancer field effect.</p><p><strong>Methods: </strong>Through a combined in silico and in vitro approach, we investigated the transcriptional dynamics of the <i>LincRNA-BC7</i>/<i>miR-663a</i>/<i>BRCA1</i> axis in response to the PARP inhibitor, Olaparib.</p><p><strong>Results: </strong>Our results demonstrate that Olaparib induces selective cytotoxicity in <i>BRCA1</i>-deficient MDA-MB-231 cells while sparing non-cancerous HEK293 cells, a response accompanied by a significant downregulation of <i>LincRNA-BC7</i> and a reciprocal upregulation of <i>BRCA1</i>. Bioinformatics analysis through BLASTN, miRBase, and KEGG revealed that <i>LincRNA-BC7</i> contains highly complementary binding sites for <i>miR-663a</i>, suggesting it functions as a competing endogenous RNA (ceRNA) or \"molecular sponge.\"</p><p><strong>Conclusions: </strong>By sequestering <i>miR-663a</i>, <i>LincRNA-BC7</i> appears to modulate the expression of critical signaling nodes within the PI3K-AKT and TP53 pathways, thereby influencing cellular sensitivity to DNA-damaging agents. These findings suggest that <i>LincRNA-BC7</i> is a key determinant of the aggressive TNBC phenotype and the response to PARP inhibition. Our study establishes the <i>LincRNA-BC7</i>/<i>miR-663a</i> axis as a novel biomarker for precision risk stratification and a promising therapeutic target to enhance treatment outcomes in <i>BRCA1</i>-associated breast cancers.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320608","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":"DNA Methylation at Birth Showing Age-Specific Association with Atopy in Children: A Prospective Longitudinal Study.","authors":"Nahid Sultana, Fen Yang, Negusse Kitaba, Stephen Potter, John W Holloway, S Hasan Arshad, Hongmei Zhang","doi":"10.3390/epigenomes10020033","DOIUrl":"10.3390/epigenomes10020033","url":null,"abstract":"<p><p><b>Background</b>: The relationship between neonatal DNA methylation (DNAm) and childhood atopy, particularly its temporal dynamics, remains inadequately characterized. Establishing this will provide insights into the epigenetic mechanisms underlying atopy development. <b>Methods</b>: Skin prick tests (SPT) for 11 common allergens were performed in the Isle of Wight third-generation birth cohort (IOWF2) at ages 1, 3, and 6 years. Atopy was defined as a positive response to one or more allergens on SPT. DNAm at birth at 294,265 CpGs from umbilical cords (<i>n</i> = 192) or Guthrie cards (<i>n</i> = 107) was screened (through R package <i>ttscreening</i>) for potential association with atopy. Pathway enrichment analysis of screened CpGs was performed using the <i>missMethyl</i> package in R. Associations between CpGs that passed screening and atopy status were assessed via logistic regressions with repeated measures, adjusting for age, sex, and birth weight. Age-specific associations were examined via DNAm × age interactions. CpGs showing age-specific association were further tested in the parental cohort (IOWBC (F1); <i>n</i> = 717). Multiple testing was controlled using FDR-adjusted <i>p</i>-values at 0.05. <b>Results</b>: In total, 601 CpGs passed screening. Pathway enrichment analysis identified enrichment of the cell activation pathway (GO:0001775; FDR-adjusted <i>p</i>-value = 0.017). DNAm at 502 CpGs in F2 showed age-specific associations with atopy. Among these, 102 CpGs showed consistent directions in F1, and 14 were statistically significant (<i>p</i>-value < 0.05). Except for cg01519508 (<i>FOXF1</i>), DNAm-atopy associations weakened over time at the remaining 13 CpGs. <b>Conclusions</b>: At certain CpGs, DNAm at birth is associated with childhood atopy in an age-dependent manner, and for CpGs showing association at an earlier age, such associations weaken at later ages.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13298419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148320735","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":"Sperm Imprinted Gene Methylation and DNA Fragmentation in ICSI Outcomes: A Pilot Study.","authors":"Anna Chiara Conflitti, Fani Konstantinidou, Alessandra Buonacquisto, Gaia Cicolani, Enrico Delli Paoli, Silvia Di Chiano, Antonella Linari, Ludovico Muzii, Serena Bianchini, Federica Quaranta, Francesco Pallotti, Francesco Lombardo, Liborio Stuppia, Valentina Gatta, Donatella Paoli","doi":"10.3390/epigenomes10020032","DOIUrl":"10.3390/epigenomes10020032","url":null,"abstract":"<p><strong>Background/objectives: </strong>Aberrant DNA methylation of imprinted genes and increased sperm DNA fragmentation (SDF) have been implicated in male infertility. However, their impact on assisted reproductive technology (ART) outcomes remains unclear. This pilot study aimed to investigate SDF and methylation status of H19, IGF2, and PEG1/MEST in relation to fertilisation and embryo development following intracytoplasmic sperm injection (ICSI).</p><p><strong>Methods: </strong>Twenty male partners of women undergoing ICSI were recruited and classified according to ART outcome into viable embryos (VEs, n = 7), non-viable embryos (NVEs, n = 7), and no fertilisation (NF, n = 6). Before sperm selection, an aliquot of each seminal sample was used for semen analysis according to WHO, 2021, SDF assessment (TUNEL assay), and sperm DNA methylation analysis of H19, IGF2, and PEG1/MEST (pyrosequencing).</p><p><strong>Results: </strong>Semen parameters were above the fifth percentile. SDF was significantly lower in the VE group compared with the other groups. H19 CpG1 methylation correlated positively with viable embryos (<i>p</i> = 0.016), while H19 CpG2 island showed a positive correlation with sperm concentration (<i>p</i> = 0.028). In male/couple infertility cases, total H19 methylation correlated negatively with SDF (<i>p</i> = 0.050). IGF2 CpG3 island methylation correlated positively with viable embryos (<i>p</i> = 0.027). Total PEG1/MEST methylation was positively correlated with fertilisation events (<i>p</i> = 0.002) and viable embryos (<i>p</i> = 0.011). PEG1/MEST CpG2 island also positively correlated with sperm motility (<i>p</i> = 0.034), while CpG3 and CpG4 showed significant correlations with fertilisation (<i>p</i> < 0.001; <i>p</i> = 0.004).</p><p><strong>Conclusions: </strong>This pilot study shows that SDF and sperm methylation levels of H19, IGF2, and PEG1/MEST are related to ICSI outcomes, supporting that sperm molecular and epigenetic features may influence fertilisation and embryo development.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037943","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":"UTY (KDM6C) in Cancer: Epigenetic Regulation, Tumour Suppressor Functions, and Clinical Implications.","authors":"Chitrakshi Chopra, Chandra Prakash Prasad, Manish Kumar","doi":"10.3390/epigenomes10020031","DOIUrl":"10.3390/epigenomes10020031","url":null,"abstract":"<p><p>The ubiquitously transcribed tetratricopeptide repeat Y-linked gene (UTY/KDM6C), a catalytically impaired histone demethylase encoded on the Y chromosome, has garnered increasing attention for its emerging roles in tumorigenesis and cancer progression. Despite high sequence homology with its X-linked paralog UTX/KDM6A, UTY exhibits markedly reduced or absent H3K27me3 demethylase activity due to critical amino acid substitutions in its Jumonji C domain. Consequently, UTY primarily functions through non-enzymatic mechanisms, acting as a scaffold in chromatin-remodelling complexes like COMPASS and SWI/SNF, or mediating protein-protein interactions that regulate transcriptional programs independent of demethylation. This aligns with epigenetic dysregulation in cancers, where imbalances in repressive H3K27me3 and active H3K4me either drive tumour suppressor silencing or oncogene activation. Unlike frequently mutated UTX in cancers such as breast, renal cell carcinoma, and acute myeloid leukaemia, UTY's contributions in cancer are less defined, constrained by male-specific expression. Emerging evidence suggests UTY as a context-dependent tumour suppressor in AML and squamous-like pancreatic ductal adenocarcinoma. While direct functional validation remains limited in several cancer types, UTY is increasingly implicated as a potential tumour suppressor in haematological malignancies and prostate cancer. Therapeutically targeting UTY's scaffold functions shows promise for male-specific cancers and merits future investigation.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037968","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":"Methadone Maintenance Treatment vs. Long-Term Abstinence Without Opioid Agonist: Epigenome-Wide Study of DNA Methylation.","authors":"Orna Levran, Justin Li, Anat Sason, Miriam Adelson, Einat Peles","doi":"10.3390/epigenomes10020029","DOIUrl":"10.3390/epigenomes10020029","url":null,"abstract":"<p><strong>Background/objectives: </strong>Opioid use disorder (OUD) is caused by a complex interplay between genetic and non-genetic factors. DNA methylation is an epigenetic mechanism that modulates gene expression. Data on DNA methylation and opioid addiction and treatment are limited. This association study was designed to assess the difference in genome-wide methylation patterns between individuals with OUD in methadone maintenance treatment (MMT) (<i>n</i> = 114) and those with OUD who achieved long-term abstinence (>10 years) without mu opioid receptor agonist treatment (<i>n</i> = 136).</p><p><strong>Methods: </strong>Differential DNA methylation analysis was performed in whole blood using the Illumina EPIC array.</p><p><strong>Results: </strong>A total of 135 differentially methylated probes (DMPs) reached epigenome-wide significance (<i>p</i> < 1 × 10^-7), controlling for sex, age, estimates of blood cell proportions, and the first two principal components based on genome-wide SNP genotypes. The methylation sites were annotated to 157 genes, including 32% long non-coding RNAs. These genes are related to several systems, including cell adhesion (e.g., <i>SAXO4</i>), immune system and inflammation (e.g., <i>UBTF</i>, <i>USP39</i>, <i>C10orf90</i>, <i>PRKCA</i>), stress response (e.g., <i>CRHR1</i>, <i>GPR19</i>), and spermatogenesis (e.g., <i>SPATA16</i>, <i>COX7B2</i>). DMP cg11641410 is located in lncRNA <i>ENSG00000254687</i>, an antisense to <i>OPRK1</i>. Six of the DMPs were also identified in a related longitudinal study of MMT.</p><p><strong>Conclusions: </strong>At this point, it is not possible to determine whether the minor methylation differences observed in this study cause clinically relevant changes in gene expression. However, these findings have the potential to identify biomarkers and to provide new targets for treatment optimization.</p>","PeriodicalId":55768,"journal":{"name":"Epigenomes","volume":"10 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13214831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037931","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}