Frontiers in epigenetics and epigenomics最新文献

{"title":"Epi-liquidomics: redefining cancer diagnostics through epigenetic profiling.","authors":"Shahper Nazeer Khan, Mohammad Harris Siddiqui, Aamir Ahmad, Luca Guarnera, Salamatu Tijjani Isah","doi":"10.3389/freae.2026.1813822","DOIUrl":"10.3389/freae.2026.1813822","url":null,"abstract":"<p><p>Early detection is central to reducing cancer related morbidity and mortality, as timely intervention significantly improves curative potential. However, conventional diagnostic modalities such as imaging and tissue biopsy often lack sensitivity for early-stage disease and are inherently invasive. To address these limitations, we introduce Epi-Liquidomics, defined as the comprehensive profiling of circulating epigenetic alterations including DNA methylation patterns, histone derived nucleosome signatures, chromatin fragmentation landscapes and non-coding RNA cargo to enable non-invasive cancer diagnostics supported by advancing technologies. Emerging preclinical and clinical evidence indicates that tumor associated DNA methylation and cfDNA fragmentation signatures are detectable even in stage I-II cancers, directly supporting their applicability in early disease identification rather than solely conceptual potential. By integrating multi-layered epigenetic signals into liquid biopsy platforms, Epi-Liquidomics enhances cancer detection in low tumor-fraction settings and enables accurate tissue-of-origin prediction, offering advantages over mutation centric genomic assays. Beyond early diagnosis, Epi-Liquidomics provides insights into tumor biology by capturing dynamic regulatory states and microenvironment-associated alterations, facilitating improved risk stratification and longitudinal disease monitoring. This framework supports real-time assessment of therapeutic response and detection of minimal residual disease. Importantly, its current limitations including false-positive rates in population screening, assay standardization, and biological variability underscore the need for rigorous prospective validation before routine clinical implementation. As sequencing technologies and computational tools continue to advance, Epi-Liquidomics holds strong translational potential to refine cancer screening and advance minimally invasive precision oncology.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1813822"},"PeriodicalIF":0.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121793","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 impact of epigenetics on tumor metabolism: Friend or foe in drug response?","authors":"Serena Castelli, Melania Franchini, Luigi Ferraro, Nicolò Mangraviti","doi":"10.3389/freae.2026.1755829","DOIUrl":"10.3389/freae.2026.1755829","url":null,"abstract":"<p><p>Cancer cells exhibit remarkable plasticity, enabling them to survive therapeutic pressure by dynamically rewiring both their epigenetic landscape and metabolic circuitry. Emerging evidence reveals that epigenetic mechanisms, including DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs, are tightly coupled to metabolic pathways through key metabolites that function as cofactors or regulators of chromatin-modifying enzymes. This reciprocal interplay establishes self-reinforcing loops that sustain tumor growth, promote heterogeneity, and drive the emergence of drug-tolerant states. In this review, we summarize current knowledge on how epigenetic remodeling shapes metabolic reprogramming and, in turn, how altered metabolite pools influence chromatin states in cancer. We highlight the central role of long non-coding RNAs and other ncRNA species in coordinating epigenetic and metabolic adaptations that underpin therapy resistance. We further examine the contribution of metabolite-dependent post-translational modifications, such as acetylation, methylation, lactylation, and succinylation, to the regulation of tumor aggressiveness and treatment response. Finally, we discuss how multi-omics integration, computational network approaches, and AI-enabled modeling are accelerating the discovery of epigenetic-metabolic vulnerabilities and informing the development of precision therapeutic strategies. Understanding and targeting this epigenetic-metabolic axis holds substantial promise for overcoming drug resistance and improving the durability of cancer therapies.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1755829"},"PeriodicalIF":0.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121830","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":"Genomic and epigenomic landscape of ADPKD: towards precision diagnostics and tailored treatments.","authors":"Amankeldi A Salybekov, Aiman Kinzhebay, Sumi Hidaka, Shuzo Kobayashi","doi":"10.3389/freae.2026.1699528","DOIUrl":"10.3389/freae.2026.1699528","url":null,"abstract":"<p><p>Autosomal dominant polycystic kidney disease (ADPKD) represents one of the most prevalent hereditary renal disorders, affecting an estimated 12.5 million individuals globally and characterized by progressive cyst formation in both kidneys. While mutations in <i>PKD1</i> and <i>PKD2</i> genes account for most cases, recent research has identified rare causative genes as contributing factors in genetically unresolved cases. The review examines the molecular mechanisms of cystogenesis, highlighting how genetic predisposition interacts with epigenetic modifications, including DNA methylation patterns, histone alterations, and non-coding RNAs (miRNAs and piRNAs). Advanced diagnostic approaches, from conventional imaging to AI-assisted cyst segmentation and long-read sequencing technologies, are evaluated for their clinical utility. Long-read sequencing platforms increase diagnostic yield by up to 25% in previously unsolved cases, while AI-enhanced imaging provides superior accuracy in disease progression monitoring. Finally, the paper explores emerging precision medicine strategies, including targeted therapies directed at specific molecular pathways, risk stratification algorithms, and personalized treatment approaches based on individual genetic and epigenetic profiles. This integration of genomic and epigenomic insights provides a foundation for improved prognostic models, early biomarkers, and tailored therapeutic interventions for ADPKD patients.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":"1699528"},"PeriodicalIF":0.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121832","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":"Metabolic reprogramming and epigenetic effects due to reducing sugars and glycation products in cancer.","authors":"Savita Bansal, Archana Burman, Taruna Arora, Meenakshi Vachher, Nalini Moza Wali, Bhupender Kumar","doi":"10.3389/freae.2025.1752493","DOIUrl":"10.3389/freae.2025.1752493","url":null,"abstract":"<p><p>Cancer cells have the ability to reprogram their metabolism to meet the proliferative and survival demands. These metabolic alterations involve the formation of many active metabolites associated with epigenetic modifications or remodelling together driving tumourigenesis through self-perpetuating feedback loops. Among the various metabolic stressors, reducing sugars, principally glucose and fructose, lactate, acetyl-CoA, glycolytic intermediates such as 3-deoxyglucosone, glyoxal, polyol pathway metabolites, and methylglyoxal effectively modulate the chromatin remodelling and gene expression. These processes lead to dysregulated DNA methylation and histone modifications involving acetylation, methylation, polysialylation, lactylation, and glycation establishing a tumourigenic environment. Elevated levels of reducing sugars and glycolytic intermediates also contribute to the formation of a large group of reactive molecules termed advanced glycation intermediates (AGIs) and advanced glycation end products (AGEs), which interact with their receptor RAGE to activate signalling cascades resulting in oxidative stress, inflammation, and aberrant gene regulation. Furthermore, the AGE-RAGE axis reprograms cancer metabolism influencing key signalling pathways including PI3K/AKT/mTOR and NF-κB. The epigenetic alterations and metabolic perturbations induced by reducing sugars and non-enzymatic glycation reactions also influence the tumour microenvironment (TME) through extracellular matrix (ECM) remodeling, angiogenesis, and immune evasion. This review elucidates the crosstalk between metabolic reprogramming, AGE-RAGE-mediated signalling, and epigenetic modulation that forms a complex network associated with cancer initiation, progression, and resistance to therapy. Understanding the molecular interplay between these pathways could pave the way for novel metabolic and epigenetic therapeutic strategies aimed at disrupting this vicious cycle and impeding tumour growth.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"3 ","pages":"1752493"},"PeriodicalIF":0.0,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121598","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":"Chromatin profiling for everyone: FFPE-CUTAC for the theory and practice of modern molecular biology.","authors":"Yiling Xu, Steven Henikoff, Kami Ahmad","doi":"10.3389/freae.2025.1753710","DOIUrl":"10.3389/freae.2025.1753710","url":null,"abstract":"<p><p>In 2025, together with the Fred Hutch Summer Undergraduate Research and Summer High School Internship programs, we developed and implemented a laboratory genomics research experience to introduce students to modern molecular biology techniques and bioinformatics. The course centered around using a new method we had developed in 2023 that uses readily available fixed tissue sections on glass slides. Students performed a series of steps to tagment genomic locations of RNA Polymerase II and then used PCR to enrich libraries for next-generation sequencing in a core facility. Students then visualized their data in genomic browser tracks and assessed the results. At the end of the summer, students prepared and presented their work and experiences in seminar format to their cohorts. Overall, the technical simplicity of on-slide chromatin profiling introduced the students to laboratory practice and current techniques in genomics, bioinformatics, and medical sciences.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"3 ","pages":"1753710"},"PeriodicalIF":0.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122009","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":"Professor Emma Whitelaw, a pioneer of epigenetic inheritance.","authors":"Alyson Ashe, Jessica J Hawes","doi":"10.3389/freae.2025.1733711","DOIUrl":"10.3389/freae.2025.1733711","url":null,"abstract":"<p><p>Here we explore the contribution of Professor Emma Whitelaw to the fields of epigenetics and transgenerational epigenetic inheritance. We highlight some recent advances to the field, while integrating the work of Professor Whitelaw and her team within our current understanding of epigenetic mechanisms.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"3 ","pages":"1733711"},"PeriodicalIF":0.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121713","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":"Comparison of enzymatic and bisulfite-based methods for sequencing-based cell-free DNA methylation profiling.","authors":"Mark Ezegbogu, Peter Averill Stockwell, Glen Reid, Ben Brockway, Rajiv Kumar, Euan Rodger, Aniruddha Chatterjee","doi":"10.3389/freae.2025.1693925","DOIUrl":"10.3389/freae.2025.1693925","url":null,"abstract":"<p><p>Epigenetic analysis, especially DNA methylation profiling of plasma cell-free DNA (cfDNA), has recently emerged as a promising clinical tool. Choosing the right analytical method is crucial for working with limited cfDNA, ensuring cost-effectiveness, and supporting clinical translation. While bisulfite-based methods have long been the standard for methylation analysis, enzymatic conversion is a potential alternative. However, their comparative performance for cfDNA remains unclear. In this study, we compared enzymatic (EM-Seq) and bisulfite-based (cfRRBS and cfMethyl-seq) methods. EM-Seq showed higher mapping efficiency, broader genomic coverage, and captured more CpGs at low coverage thresholds, while the bisulfite methods had higher conversion rates, lower costs, and better coverage of functional regions like promoters and exons. The bisulfite-based methods also demonstrated superior reproducibility. Overall, cfRRBS offered the best balance of cost, accuracy, and reproducibility. Our findings fill a key gap in cancer epigenetics, outline the strengths and limitations of each method, and provide a practical guide for selecting cfDNA methylation profiling methods in liquid biopsy applications.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"3 ","pages":"1693925"},"PeriodicalIF":0.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121931","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":"A placental DNA methylation score associated with early-onset preeclampsia and maternal vascular malperfusion pathology.","authors":"Hannah J Illing, Alexa A Freedman, Lauren Keenan-Devlin, Gregory E Miller, Ann E Borders, Linda M Ernst, Wendy P Robinson","doi":"10.3389/freae.2026.1749513","DOIUrl":"10.3389/freae.2026.1749513","url":null,"abstract":"<p><strong>Introduction: </strong>Early-onset preeclampsia (EOPE) is a severe maternal hypertensive disorder of pregnancy, where placental dysfunction is a component of the pathophysiology. Previously, we developed the eoPRED tool, which is a DNA methylation (DNAme)-based method that estimates the likelihood that a placenta came from a pregnancy complicated by EOPE. We hypothesize that this score may reflect maternal vascular malperfusion (MVM), which is the most common placental pathology observed in early-onset preeclampsia (EOPE), but is also associated with preterm birth and fetal growth restriction. To test this we evaluated whether eoPRED score is associated with the severity of MVM pathology in placentas from both preeclamptic and non-preeclamptic pregnancies.</p><p><strong>Methods: </strong>We utilized 493 placentas with both Infinium EPICv1.0 DNA methylation data and histopathologic characterization by a placental pathologist. We evaluated associations between eoPRED score and four major classes of placental pathology: maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), chronic inflammation (CI), and acute inflammation (AI).</p><p><strong>Results: </strong>eoPRED score was higher in placentas from pregnancies with EOPE (n = 7) than controls without preeclampsia (n = 402, p < 0.001). Independent of EOPE, eoPRED correlated with the grade of MVM (R = 0.34, p < 0.01), but was not associated with any other pathology class.</p><p><strong>Discussion: </strong>eoPRED score can not only be used to identify cases of likely EOPE but is also associated with placental maternal vascular dysfunction in the absence of preeclampsia. This score may thus be useful in placental DNAme datasets lacking pathology information to identify associations between exposures/and or birth outcomes with placental dysfunction.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13441432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681607","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 pioneering work of Howard Cedar and his team in unraveling the roles DNA methylation plays in regulating genome function.","authors":"Eugin Destici, Eric Mendenhall, Alon Goren","doi":"10.3389/freae.2026.1754553","DOIUrl":"10.3389/freae.2026.1754553","url":null,"abstract":"<p><p>The covalent modification of specific DNA nucleotides by addition of a methyl group, termed DNA methylation, was observed in bacteria in 1925 and in mammals in 1948. Yet, the function of this modification was uncertain for many years, particularly its roles in mammalian cells. During the past five decades, work from Howard Cedar and his lab has provided fundamental and groundbreaking insight into the role DNA methylation plays in regulating gene expression in health and disease. Using simple yet elegant experiments, Cedar and his team provided unequivocal evidence for the direct role of DNA methylation in transcription regulation, and demonstrated that DNA methylation serves as a stable heritable epigenetic mark. Building on these foundational discoveries, Howard Cedar and his team have further illuminated the critical role of DNA methylation in organismal development and cellular function, as well as the contribution of altered DNA methylation to cancer. Further, Cedar and his lab also demonstrated that the developmentally regulated removal of DNA methylation is pre-programmed in the genome via sequence motifs that recruit trans-acting factors at specific developmental phases. Howard Cedar's pioneering scientific contributions have resulted in paradigm shifts in the study of transcription as well as DNA replication and set up the groundwork for fields of research that continue to thrive and expand into areas such as diagnostics, modeling of aging and targeted treatments.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13344417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148414487","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":"Histones deacetylases in the epidermis: structure, functions and therapeutic implications.","authors":"Chloé Nguyen Van, Jérôme Lamartine","doi":"10.3389/freae.2025.1711733","DOIUrl":"10.3389/freae.2025.1711733","url":null,"abstract":"<p><p>Histone deacetylases (HDACs) are key epigenetic regulators that catalyze the removal of acetyl groups from histones and non-histone proteins, thereby modulating chromatin accessibility and gene expression. The HDAC family is composed of 11 HDACs and seven sirtuins that are all located within the epidermis. These enzymes are involved in essential cellular processes such as proliferation, differentiation, the regulation of immune function and wound healing, thus playing a central role in maintaining tissue homeostasis. This review aims to explore the mechanistic contributions of HDACs to epidermis physiology and investigate their involvement in the development of diseases such as psoriasis, atopic dermatitis and cancers. It also highlights the therapeutic potential of HDAC inhibitors, which are already used in oncology but whose application in dermatology is still emerging.</p>","PeriodicalId":101353,"journal":{"name":"Frontiers in epigenetics and epigenomics","volume":"3 ","pages":"1711733"},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149121539","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}