Frontiers in epigenetics and epigenomics最新文献

{"title":"MeCP2 functions as a DNA methylation reader in immune homeostasis and cancer.","authors":"Grace C Stroman, Clara Mellows, Kevin Pruitt","doi":"10.3389/freae.2026.1917394","DOIUrl":"10.3389/freae.2026.1917394","url":null,"abstract":"<p><p>DNA methylation is a key epigenetic mechanism that mediates gene expression and informs cellular identity. Methyl-CpG binding protein 2 (MeCP2) is a protein capable of recognizing and interpreting the methylated DNA code to bring about phenotypic outcomes through co-factor interactions. Altered DNA methylation patterns and MeCP2 function, therefore, disrupt cellular epigenetic homeostasis and contribute to human diseases. MeCP2 loss-of-function or amplification events are responsible for Rett syndrome and <i>MECP2</i> duplication syndrome, respectively, where patients present with multisystem pathophysiology. Growing evidence suggests that MeCP2 contributes to immune dysregulation in these syndromes and is a key epigenetic regulator in additional inflammatory conditions. Research in past decades has functionally linked MeCP2 to tumorigenesis across cancer types, where it can support and inhibit oncogenic properties in a contextual manner. The precise mechanistic role of MeCP2 in non-neuronal and cancer models is underexplored. Here, we summarize the diverse epigenetic functionalities of MeCP2 influenced by its molecular structure, regulation, and co-factor interactions and discuss how MeCP2 regulates immune homeostasis and tumorigenesis.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1917394"},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121843","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":"From chromatin to proteostasis: multilevel gene regulation in Mendelian diseases.","authors":"Himanshu Goel, Gunjan Garg","doi":"10.3389/freae.2026.1944086","DOIUrl":"10.3389/freae.2026.1944086","url":null,"abstract":"<p><p>Pathogenic variation can alter gene output at multiple levels, from chromatin accessibility and enhancer-promoter communication to RNA processing, translation and protein turnover. The diagnostic challenge is not to catalogue these layers, but to determine which regulatory mechanism is plausible for a given variant, phenotype, tissue and developmental context. This targeted narrative review synthesises representative Mendelian mechanisms across five linked levels: chromatin, transcription, RNA processing and stability, translation, and post-translational proteostasis. Three cross-cutting principles recur. First, distinct molecular lesions may converge on the same functional bottleneck: altered dosage, timing, localisation or disrupted protein homeostasis. Second, regulatory effects are often cell-type-, isoform-, developmental-stage- and state-specific, so assay and tissue selection are integral to interpretation. Third, a negative result in an accessible surrogate such as blood does not exclude a disease-relevant effect in brain, muscle, liver or stimulated immune cells. From these principles, the review derives a mechanism-directed diagnostic framework that links variant class to orthogonal assays, including DNA methylation profiling, chromatin and reporter assays, RNA sequencing, ribosome-level methods and protein-based studies. The framework is offered as an integrative clinical synthesis rather than a new model of gene regulation, to support variant interpretation, functional-test selection and translational prioritisation in unsolved Mendelian disease.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1944086"},"PeriodicalIF":0.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121824","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":"Circular RNAs: from transcriptional noise to engineered therapeutics.","authors":"Aaron C Chack, Chad V Pecot","doi":"10.3389/freae.2026.1894220","DOIUrl":"10.3389/freae.2026.1894220","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are single stranded, closed, primarily non-coding RNA circles that have risen to the forefront of the non-coding RNA field. Studies from recent years have shown that circRNAs are produced from endogenous, non-canonical RNA splicing mechanisms, demonstrate specific cellular localizations, regulation by RNA modifications and function in many fundamental and critical cellular processes. CircRNAs can influence gene expression both pre- and post-transcriptionally, influence translation and interact with cellular RNA and proteins to enable cellular homeostasis. Aberrations in circRNA expression patterns lead to alterations in gene regulatory networks, which have been implicated in the progression of many cancer types. Unique characteristics of circRNAs, particularly their stability within cells and ability to be leveraged for protein production, have led to the engineering of artificial circRNAs to be used as an emerging therapeutic modality. Here we review how circRNAs regulate homeostasis in normal tissues, how dysregulated expression of circRNAs impacts various cancers and emerging therapeutic technologies that build upon their unique features.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1894220"},"PeriodicalIF":0.0,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121730","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":"Arsenic induced Hippo pathway dysregulation linked to hTERT hypo-methylation in breast cancer patients.","authors":"Archana Chaudhary, Manish Kumar, Lalit Mohan, Abhay Kumar, Rishikesh Kumar, Shailesh Kumar, Kumar Pranay, Nandani Kumari, Rizwanul Haque, Md Margoob Ahmad","doi":"10.3389/freae.2026.1853054","DOIUrl":"10.3389/freae.2026.1853054","url":null,"abstract":"<p><strong>Introduction: </strong>A key stage in the development of almost all types of malignancies is the dysregulation of telomeres and telomerase (hTERT). It has been suggested that arsenic-mediated changes in gene methylation status can mute tumor suppressor genes or increase oncogene expression, resulting in long-term alterations in the activity of genes governing cell transformation. Recent study demonstrated that, long-term exposure to an environmentally relevant dose of arsenic affects cellular development by interfering with the Hippo signaling system. The current study's objective is to ascertain the underlying molecular cause of arsenic induced telomerase alteration and how it is associated with gene methylation.</p><p><strong>Method: </strong>Twenty-eight female with intermittent breast cancer from arsenic exposed areas were selected, after surgery, a sample of the tumor and the healthy tissue (which serves as a control group) were extracted for further processing. Arsenic concentration was analyzed by atomic absorption spectrometry. Western blotting and RT-PCR were used to analyze the telomerase expression. Additionally, MS-PCR was used to identify the genetic and epigenetic changes, respectively.</p><p><strong>Result: </strong>According to our research, 65% of female breast cancer patients had extremely high arsenic concentrations with elevated telomerase expression. The cause of this up regulation of telomerase expression is hTERT promoter hypomethylation.</p><p><strong>Discussion: </strong>The findings also demonstrated a substantial association between breast cancer patients' upregulation of hTERT and their exposure to arsenic and fine-needle biopsy specimens may provide further predictive information. Higher telomerase expression was associated with a worse outcome.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1853054"},"PeriodicalIF":0.0,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121733","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":"Phenotypic plasticity in fish cell lines: conceptual links to aquatic epigenetics.","authors":"Daisuke Ikeda","doi":"10.3389/freae.2026.1867376","DOIUrl":"10.3389/freae.2026.1867376","url":null,"abstract":"<p><p>Fish cell lines have long supported aquatic research, yet their emerging role as seed cells for cultured seafood requires a deeper understanding of their phenotypic stability. Although these cells often demonstrate prolonged proliferation and relative resistance to culture-associated senescence, they can also exhibit marked culture-dependent variability. In this review, I examine a central feature of fish cell culture: the coexistence of durable growth and flexible cell states. By focusing on spontaneous immortalization, passage-dependent changes, and differentiation-related plasticity, particularly in muscle and adipose lineages, I consider how these phenomena may be interpreted through the lens of epigenetic plasticity. Direct epigenomic evidence remains limited, and this review therefore presents a hypothesis-generating conceptual framework rather than an established mechanistic model. Nevertheless, studies involving DNA demethylation, incomplete senescence programs, possible differences in senescence-related genomic context, environmental epigenetics, and nuclear organization provide conceptual clues that reversible regulatory processes above the level of DNA sequence may shape fish cell-state behavior. I further discuss how this perspective is relevant to aquatic biotechnology and cultured seafood, where reproducibility, lineage control, quality control, and process standardization depend on monitoring cell-state behavior while distinguishing reversible regulatory changes from genetic alterations acquired during long-term culture. Clarifying the regulatory processes associated with phenotypic plasticity in fish cell lines may therefore provide a useful foundation for future epigenomic studies and for the development of biologically reliable fish cell platforms.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1867376"},"PeriodicalIF":0.0,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121875","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":"Elucidation of chromatin loops among regulatory regions using Hi-TrAC.","authors":"Yaqiang Cao, Qingsong Tang, Keji Zhao","doi":"10.3389/freae.2026.1858923","DOIUrl":"10.3389/freae.2026.1858923","url":null,"abstract":"<p><p>Cellular development and differentiation are critically regulated by the spatiotemporal expression of genes within the genome, which are packaged into a highly organized chromatin structure. Genes in the human genome are often regulated by long-distance promoter-enhancer interactions. To better understand gene expression regulation, it is essential to identify specific interactions between distal <i>cis</i>-regulatory elements and their target promoters. To this end, we developed Hi-TrAC, a technique that generates high-resolution interaction maps among accessible chromatin regions without relying on <i>in vitro</i> proximity ligation, while maintaining low sequencing cost. In addition, Hi-TrAC provides a genome-wide landscape of chromatin accessibility. In this article, we present a robust detailed protocol for performing Hi-TrAC assay.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1858923"},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121738","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 microbiome and its impact on the epigenome in cancer.","authors":"Akhil Kapoor, Rohit Kumar, Anuj Gupta, Bipinesh Sansar, Bal Krishna Mishra, Mahesh Chaudhary, Archi Rungta, Gopalakrishna Kallapura, Kumar Prabhash","doi":"10.3389/freae.2026.1857307","DOIUrl":"10.3389/freae.2026.1857307","url":null,"abstract":"<p><p>The complex interplay between the human microbiome and epigenetic regulation represents one of the most rapidly evolving frontiers in cancer biology. The trillions of microorganisms residing in and on the human body collectively termed the microbiota may influence the host gene expression through epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation. In cancer patients, is associated with disruption of the normal epigenetic landscape, contributing to oncogenesis, tumor progression, immune evasion, and therapeutic resistance. This review synthesizes current evidence on how specific microbial metabolites such as short-chain fatty acids, secondary bile acids, and folate derivatives modulate epigenetic marks in tumor cells and the tumor microenvironment. We further discuss the emerging concept of the \"oncobiome\" and examine how microbiome-epigenome crosstalk influences cancer risk, progression, and response to therapy including chemotherapy, immunotherapy, and epigenetic drugs. Finally, we explore the translational potential of microbiome modulation as an adjunct strategy in cancer epigenomics, highlighting key research gaps and future directions.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1857307"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121906","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":"Editorial: Epigenetics and metabolism: a closed liaison in tumor cells.","authors":"Serena Castelli, Nicolò Mangraviti, Rohan Kodgule","doi":"10.3389/freae.2026.1886632","DOIUrl":"10.3389/freae.2026.1886632","url":null,"abstract":"","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1886632"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121773","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":"Environmental epigenetic modifiers in neurodegenerative diseases: a systematic review of epigenomic mechanisms and therapeutic targets.","authors":"Pranay Wal, Sunita Mishra, Debashish Pradhan, Ankita Wal, Debashis Purohit, Lalit Mohan Nainwal, Vivek Dhir, Amin Gasmi","doi":"10.3389/freae.2026.1833533","DOIUrl":"10.3389/freae.2026.1833533","url":null,"abstract":"<p><strong>Background: </strong>Environmental contaminants and neurotoxicants are becoming more widely acknowledged as major causes of neurodegenerative illnesses due to systemic biological disruption including oxidative stress, mitochondrial dysfunction, chronic neuroinflammation, and chromatin remodeling-associated epigenetic dysregulation epigenetic modification. According to new research, exposures to heavy metals, gaseous pollutants, particulate matter, and synthetic neurotoxicants alter gene-regulatory networks and accelerate neurodegenerative processes.</p><p><strong>Objective: </strong>With an emphasis on molecular mechanisms, developmental neurotoxicity, and translational pathways connecting environmental exposures with epigenomic changes and neurological outcomes, the goal of this systematic review is to compile the most recent data on environmental epigenetic modifiers in neurodegenerative diseases.</p><p><strong>Method: </strong>Using structured searches across major biomedical databases, the review was carried out in accordance with PRISMA principles. A multistage selection procedure was used to evaluate studies that addressed environmental neurotoxicants, epigenetic processes (DNA methylation, histone modification, and non-coding RNAs), and neurodegenerative consequences. To find common routes and life-course exposure effects, relevant experimental, epidemiological, mechanistic, and translational data were qualitatively summarized.</p><p><strong>Results: </strong>The findings of the included research show that exposure to the environment causes oxidative stress, mitochondrial dysfunction, neuroinflammation, and chromatin remodeling. These effects result in alterations in histone acetylation, DNA methylation patterns, and dysregulated expression of microRNAs. Amyloidogenic signaling, synaptic dysfunction, and neuronal death were consistently linked to both chemical and particulate matter neurotoxicants. Furthermore, early environmental stressors create long-term epigenetic programming that heightens vulnerability to eventual neurodegenerative pathology, according to developmental exposure models.</p><p><strong>Conclusion: </strong>An important link between the exposome and the risk of neurodegenerative diseases is represented by environmental epigenetic modifiers. Epigenetic pathways including histone acetylation imbalance, microRNA-mediated regulation (e.g., miR-574-5p), and DNA methylation changes emerge as potential biomarkers and therapeutic targets. Future research should prioritizemulti-omics techniques, harmonized exposure assessment, and longitudinal human investigations to advance precision prevention and intervention strategies.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1833533"},"PeriodicalIF":0.0,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121765","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":"Mobile small RNAs as mediators of stress-induced epigenomic remodeling and systemic stress adaptation.","authors":"Muhammad Daniyal Junaid, Muhammad Shahzad Iqbal, Muhammad Waqar Nasir, Muhammad Waseem Akhter","doi":"10.3389/freae.2026.1827933","DOIUrl":"10.3389/freae.2026.1827933","url":null,"abstract":"<p><p>Plants rely on sophisticated long-distance communication networks to coordinate adaptive responses to changing environmental conditions. Among these, mobile small RNAs (sRNAs), including microRNAs (miRNAs) and small interfering RNAs (siRNAs), function as critical systemic signaling molecules that move between tissues through plasmodesmata and the phloem. While their roles in post-transcriptional gene regulation are well established, emerging evidence indicates that mobile sRNAs also mediate stress-induced epigenomic remodeling in recipient tissues. Specifically, 24-nt siRNAs can direct RNA-dependent DNA methylation (RdDM) and chromatin modifications at distal genomic loci, thereby altering transcriptional states, stabilizing stress-responsive gene networks, and modulating transposon activity. Such epigenetic reprogramming can extend beyond transient stress responses, contributing to stress memory and, in some cases, to transgenerational inheritance of adaptive traits. This review synthesizes current knowledge on the biogenesis, transport, and functional integration of mobile sRNAs, with special emphasis on their capacity to reshape DNA methylation landscapes and chromatin architecture during environmental stress. We further discuss experimental evidence from grafting studies, methylome profiling, and mutant analyses that support systemic epigenetic regulation mediated by sRNAs. Finally, we explore the practical applications of leveraging mobile sRNA-driven epigenomic remodeling for sustainable crop improvement, including epi-grafting and targeted epigenome engineering strategies. By positioning mobile sRNAs as mediators of systemic epigenetic plasticity, this review emphasizes their central role in coordinating plant stress adaptation in a changing climate.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1827933"},"PeriodicalIF":0.0,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121896","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}