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        <title>Frontiers in Epigenetics and Epigenomics | New and Recent Articles</title>
        <link>https://www.frontiersin.org/journals/epigenetics-and-epigenomics</link>
        <description>RSS Feed for Frontiers in Epigenetics and Epigenomics | New and Recent Articles</description>
        <language>en-us</language>
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        <pubDate>2026-05-14T05:34:38.177+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2026.1827933</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2026.1827933</link>
        <title><![CDATA[Mobile small RNAs as mediators of stress-induced epigenomic remodeling and systemic stress adaptation]]></title>
        <pubdate>2026-05-07T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Muhammad Daniyal Junaid</author><author>Muhammad Shahzad Iqbal</author><author>Muhammad Waqar Nasir</author><author>Muhammad Waseem Akhter</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2026.1754553</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2026.1754553</link>
        <title><![CDATA[The pioneering work of Howard Cedar and his team in unraveling the roles DNA methylation plays in regulating genome function]]></title>
        <pubdate>2026-04-14T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Eugin Destici</author><author>Eric Mendenhall</author><author>Alon Goren</author>
        <description><![CDATA[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 5 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2026.1813822</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2026.1813822</link>
        <title><![CDATA[Epi-liquidomics: redefining cancer diagnostics through epigenetic profiling]]></title>
        <pubdate>2026-04-10T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Shahper Nazeer Khan</author><author>Mohammad Harris Siddiqui</author><author>Aamir Ahmad</author><author>Luca Guarnera</author><author>Salamatu Tijjani Isah</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2026.1755829</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2026.1755829</link>
        <title><![CDATA[The impact of epigenetics on tumor metabolism: Friend or foe in drug response?]]></title>
        <pubdate>2026-02-09T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Serena Castelli</author><author>Melania Franchini</author><author>Luigi Ferraro</author><author>Nicolò Mangraviti</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2026.1699528</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2026.1699528</link>
        <title><![CDATA[Genomic and epigenomic landscape of ADPKD: towards precision diagnostics and tailored treatments]]></title>
        <pubdate>2026-02-06T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Amankeldi A. Salybekov</author><author>Aiman Kinzhebay</author><author>Sumi Hidaka</author><author>Shuzo Kobayashi</author>
        <description><![CDATA[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 PKD1 and PKD2 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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1752493</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1752493</link>
        <title><![CDATA[Metabolic reprogramming and epigenetic effects due to reducing sugars and glycation products in cancer]]></title>
        <pubdate>2026-01-27T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Savita Bansal</author><author>Archana Burman</author><author>Taruna Arora</author><author>Meenakshi Vachher</author><author>Nalini Moza Wali</author><author>Bhupender Kumar</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1753710</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1753710</link>
        <title><![CDATA[Chromatin profiling for everyone: FFPE-CUTAC for the theory and practice of modern molecular biology]]></title>
        <pubdate>2026-01-26T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yiling Xu</author><author>Steven Henikoff</author><author>Kami Ahmad</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1733711</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1733711</link>
        <title><![CDATA[Professor Emma Whitelaw, a pioneer of epigenetic inheritance]]></title>
        <pubdate>2026-01-20T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Alyson Ashe</author><author>Jessica J Hawes</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1693925</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1693925</link>
        <title><![CDATA[Comparison of enzymatic and bisulfite-based methods for sequencing-based cell-free DNA methylation profiling]]></title>
        <pubdate>2026-01-16T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Mark Ezegbogu</author><author>Peter Averill Stockwell</author><author>Glen Reid</author><author>Ben Brockway</author><author>Rajiv Kumar</author><author>Euan Rodger</author><author>Aniruddha Chatterjee</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1711733</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1711733</link>
        <title><![CDATA[Histones deacetylases in the epidermis: structure, functions and therapeutic implications]]></title>
        <pubdate>2025-12-08T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Chloé Nguyen Van</author><author>Jérôme Lamartine</author>
        <description><![CDATA[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.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1644521</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1644521</link>
        <title><![CDATA[Epigenetic profiling of preterm birth: a dual-tissue methylation patterns using long-read sequencing]]></title>
        <pubdate>2025-12-05T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>BalaSubramani Gattu Linga</author><author>Faisal E. Ibrahim</author><author>Aleem Razzaq</author><author>Muthanna Samara</author><author>Jameela Roshanuddin</author><author>Hind H. Adi</author><author>Aseel Al-Dewik</author><author>Ayla J. Ahmedoglu</author><author>Rand Hamdan</author><author>Amal E. I. Ahmed</author><author>M. Walid Qoronfleh</author><author>Hatem Zayed</author><author>Duaa Elshiekh</author><author>Mona Ellaithi</author><author>Mohamed Alsharshani</author><author>Palli Valapila Abdulrouf</author><author>Thomas Farrell</author><author>Bader Kurdi</author><author>Ghassan Abdoh</author><author>Hilal Al Rifai</author><author>Nader Al-Dewik</author>
        <description><![CDATA[IntroductionPreterm birth (PTB), a leading cause of neonatal morbidity and mortality, arises from complex maternal-fetal interactions with multifactorial origins. Emerging evidence suggests that epigenetic dysregulation may mediate these interactions. This study aimed to identify DNA methylation changes associated with PTB to uncover potential biomarkers and underlying mechanisms.MethodsWe employed long-read sequencing to profile genome-wide DNA methylation followed by gene ontology and pathway enrichment analysis in matched maternal peripheral blood and neonatal cord blood from 15 preterm and 7 full-term deliveries (mother–infant pairs).ResultsA total of 1,151 significantly differentially methylated regions (DMRs) and 25,336 differentially methylated loci (DMLs) were identified across maternal and neonatal blood samples. In maternal blood from PTB cases, the most significantly hypermethylated genes were MED38, PSMB11, and WNT7B, whereas EXTL3 and MMP9 were among the most hypomethylated. Additionally, the promoters of VWA5A, EIF4E3, ZNF571, and COPB2 exhibited significant hypermethylation, while those of SIRPB1 and TNFRSF19 showed hypomethylation. In neonatal cord blood from PTB cases, the most significantly hypermethylated genes were LOC401478, ISG20, LMTK3, TCAF2, and COL4A2, whereas EXTL3 and MMP9 were among the most hypomethylated. Promoters of DKK3, CELF2, and IFI35 were notably hypermethylated, whereas ALOX12 and CLBA1 were among the most hypomethylated. Enrichment analysis revealed that these epigenetic alterations impact critical developmental, immune, and neuroendocrine pathways, including Wnt signaling, calcium signaling, MAPK, oxytocin signaling, and neuroactive ligand-receptor interaction. Comparative analysis identified 120 overlapping DMLs, with 91 hypermethylated and 28 hypomethylated consistently across maternal and neonatal samples, including DPPA3, ABCA1, and GKN1. In contrast, 20,240 and 4,770 DMLs were unique to cord and peripheral blood, respectively. Additionally, 14 overlapping DMRs were mapped to genes such as PLD5, FBXO40, GMNC, HHIP, CLEC18B, and LHX1, exhibiting non-random chromosomal clustering. Enrichment analysis of these shared DMRs revealed significant involvement in developmental processes, including skeletal morphogenesis, axis patterning, and fibroblast growth factor signaling, indicating convergence on core regulatory pathways in PTB.ConclusionThis is the first dual-tissue PTB study using long-read methylation profiling. Our results reveal distinct and shared epigenetic signatures in maternal and neonatal compartments, offering insights into the molecular etiology of PTB and potential biomarkers for early detection and therapeutic intervention.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1723159</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1723159</link>
        <title><![CDATA[Epigenetic dysregulation in pancreatic cancer: emerging biomarkers and clinical applications]]></title>
        <pubdate>2025-11-27T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Hina Sultana</author><author>Abhishikt David Solomon</author><author>Atif Khurshid Wani</author><author>Surendra K. Shukla</author>
        <description><![CDATA[Pancreatic cancer, in particular pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal malignancies with delayed diagnosis, aggressive nature, and profound therapeutic resistance. Recent research has emphasized epigenetic dysregulation not as a bystander but as a driving force in pancreatic tumorigenesis, progression, metastasis, and immune evasion. This review presents a detailed analysis of the multifaceted functions of epigenetic mechanisms like DNA methylation, histone modifications, and non-coding RNAs in shaping the pancreatic cancer epigenome. We discuss how these alterations fuel tumor heterogeneity, modulate the tumor microenvironment, and interact with key oncogenic mutations like KRAS and TP53. Further, we discuss the potential of epigenetic alterations as diagnostic, prognostic, and predictive biomarkers with an emphasis on their application in liquid biopsies. Finally, we evaluate current and prospective epigenetic therapies, their cooperation with chemotherapy and immunotherapy, and the prospects of new approaches such as CRISPR-based epigenome editing and personalized epigenetic profiling. Together, these findings point to the epigenome as a powerful window of opportunity for understanding, diagnosing, and eventually targeting pancreatic cancer.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1736716</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1736716</link>
        <title><![CDATA[Editorial: Epigenetic basis of circadian rhythm and metabolism]]></title>
        <pubdate>2025-11-18T00:00:00Z</pubdate>
        <category>Editorial</category>
        <author>Rasime Kalkan</author><author>Peter S. Reinach</author><author>Zachary Harvanek</author><author>Dongsheng Yan</author>
        <description></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1691949</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1691949</link>
        <title><![CDATA[Epigenetic repurposing of carbohydrate metabolic inhibitors for insulin resistance: targeting DNMT1 and HDAC3 for β-cell restoration]]></title>
        <pubdate>2025-10-30T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Muhammad Javid Iqbal</author><author>Luis A. Salazar</author>
        <description><![CDATA[Insulin resistance, a global metabolic crisis affecting a substantial portion of the world’s population, involves complex metabolic-epigenetic crosstalk that current therapies fail to address. DNA methyltransferase 1 (DNMT1) and histone deacetylase 3 (HDAC3) progressively silence insulin signaling genes, creating a self-perpetuating cycle of metabolic dysfunction. We present a hypothetical cross-target repurposing strategy leveraging established α-amylase and α-glucosidase inhibitors as potential epigenetic modulators. Through systematic computational screening of 100 natural metabolic enzyme inhibitors against DNMT1 and HDAC3 crystal structures (PBD ID: 3PTA, 4A69), we identified ten dual-target candidates with binding affinities ranging from −8.1 to −10.2 kcal/mol. Kotalanol emerged as the lead compound, demonstrating strong binding to both HDAC3 (−9.8 kcal/mol) and DNMT1 (−10.2 kcal/mol). Molecular docking revealed that polyphenolic metabolic inhibitors share structural features enabling interaction with epigenetic enzyme active sites, particularly zinc-binding motifs and aromatic pockets. ADMET profiling confirmed favorable pharmacokinetic properties for the top candidates. Clinically validated compounds including berberine, curcumin, and EGCG provide proof-of-concept for dual metabolic-epigenetic activity. This repurposing approach offers significant advantages: utilizing compounds with established safety profiles, addressing multiple pathogenic mechanisms simultaneously, and accelerating therapeutic development. By targeting both immediate glucose control and long-term epigenetic preservation, these dual-action compounds could transform diabetes management from symptomatic treatment to mechanistic intervention, potentially reversing insulin resistance progression rather than merely managing hyperglycemia.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1699969</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1699969</link>
        <title><![CDATA[Non-coding RNAs at the intersection of epigenetics and cancer metabolism]]></title>
        <pubdate>2025-10-20T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Nicolò Mangraviti</author><author>Serena Castelli</author>
        <description><![CDATA[Cancer cells are primarily characterized by uncontrolled proliferation, which is closely linked to an increased energy demand. According to this, cancer cells preferentially utilize the glycolytic pathway for energy production. Metabolic regulation in cancer occurs at multiple levels, including post-translational modifications, which are rapid and energy-efficient, as they do not require enzyme degradation. In this context, non-coding RNA-mediated control plays a crucial role, as these small RNAs can directly modulate the mRNAs of key metabolic enzymes or induce epigenetic modulations, ultimately inducing alterations in cancer metabolism. In this mini-review, we summarize how non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), modulate core metabolic pathways, including glycolysis, mitochondrial respiration, lipid metabolism, and amino acid biosynthesis, in cancer. We also highlight recent findings that uncover novel regulatory mechanisms and propose that ncRNAs serve as dynamic integrators of metabolic and oncogenic signals. Understanding these interactions may open new avenues for biomarker identification and ncRNAs-targeted therapies development.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1638572</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1638572</link>
        <title><![CDATA[Cancer metabolism rewiring and chromatin methylation: a vulnerable epi-metabolic link]]></title>
        <pubdate>2025-08-25T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Sandra Atlante</author><author>Veronica Barbi</author><author>Carlo Gaetano</author><author>Barbara Illi</author>
        <description><![CDATA[Over the past few years, significant advances have been made in understanding the crosstalk between cancer metabolism and gene expression. Whereas higher levels of expression of metabolic enzymes may be considered a conceivable compensatory mechanism to satisfy the increasing request of energy of tumor cells, the detection of changes in the amount and species of intermediate metabolites (oncometabolites) and the discovery of their functional role as co-factors and structural components of chromatin modifiers tightened the link between metabolic shifts and epigenome reshaping in cancer. Changes in the chromatin methylation landscape are one of the epigenetic fingerprints of cancer metabolic rewiring associated with the tumorigenic features of neoplasms. Thus, we propose targeting metabolic enzymes directly involved in cancer methylome remodeling and oncometabolite-dependent chromatin modifiers as innovative tools to reset the epigenome of deregulated cancer cells.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1648270</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1648270</link>
        <title><![CDATA[Pioneers of chromosome elimination]]></title>
        <pubdate>2025-07-29T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Luca Comai</author><author>Mohan Prem Anand Marimuthu</author>
        <description><![CDATA[Epigenetic traits are persistent cellular and organismal properties that do not result from changes in DNA sequence. One such property involves transmission of chromosomes, which entails the formation of highly specialized chromatin structures, the kinetochores, on selected chromosomal regions, called centromeres. Centromere function is essential and centromeres are determined epigenetically by the deposition of a variant histone H3 CENP-A (CENH3 in plants). Either reduced or ectopic function alone leads to genome instability, decreased fitness, aneuploid syndromes, and cancer. At times, however, centromeres malfunction in an apparently programmed mode. This is exemplified by a peculiar centromeric syndrome involving selective elimination of a chromosome set, which can affect a wide range of organisms, including plants. Over half a century ago, plant geneticists described this syndrome in interspecific crosses of barley. Building on their work, we examine the growing understanding of how CENH3 function can be modified to affect epigenetic regulation of centromeres.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1594400</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1594400</link>
        <title><![CDATA[Discovery and structural studies of histone demethylases]]></title>
        <pubdate>2025-05-30T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Longfei Peng</author><author>Xinze Li</author><author>Hao Yang</author><author>Haonan Chen</author><author>Yue Yang</author><author>Shunfeng Peng</author>
        <description><![CDATA[The discovery and structural elucidation of histone demethylases represent a groundbreaking advancement in the field of epigenetics. Histone methylation, a critical chromatin modification, was long regarded as irreversible until the identification of histone demethylases overturned this paradigm. In 2004, the discovery of the first histone demethylase, LSD1 (Lysine-Specific Demethylase 1), unveiled the dynamic regulatory mechanisms governing methylation modifications. Subsequent identification of the JmjC domain-containing demethylase family further expanded the diversity and functional repertoire of these enzymes. Structural biology studies have revealed the molecular mechanisms by which these enzymes remove methyl groups via oxidation or hydroxylation reactions, providing key insights into their substrate specificity and catalytic processes. This article will provide a concise overview of the discovery history, fundamental structures, and functional mechanisms of histone demethylases, summarize research progress on identified histone demethylases, and offer novel insights and offer novel insights and suggestions for fundamental research on sites where demethylases remain undiscovered.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1519449</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1519449</link>
        <title><![CDATA[Epigenetic mechanisms of plasticity and resistance in glioblastoma: therapeutic targets and implications]]></title>
        <pubdate>2025-05-16T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Farzaneh Amirmahani</author><author>Saurav Kumar</author><author>Sree Deepthi Muthukrishnan</author>
        <description><![CDATA[Glioblastoma (GBM), a highly aggressive and malignant form of primary adult brain cancer, poses significant therapeutic challenges. Despite our improved understanding of the cellular and molecular mechanisms underlying tumorigenesis and the evolution of GBM, targeted molecular therapies have failed to improve patient survival outcomes. The failure of standard treatments and targeted therapies is mainly attributed to the acquisition of phenotypic plasticity of tumor cells and GBM stem-like cells. Epigenetic modifications and their mediators have emerged as crucial regulators of phenotypic plasticity, influencing tumor heterogeneity, therapy resistance and disease progression. Here, we summarize and provide insights into epigenetic regulation of GBM plasticity and specifically, focus on the roles played by DNA- and histone modifiers and non-coding RNAs in driving phenotypic plasticity and resistance. We also delve into their dynamics in response to standard therapies and the challenges for targeting them to overcome phenotypic plasticity and resistance in GBM.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.frontiersin.org/articles/10.3389/freae.2025.1607433</guid>
        <link>https://www.frontiersin.org/articles/10.3389/freae.2025.1607433</link>
        <title><![CDATA[Hansemann’s anaplastic theory of cancer after 135 years]]></title>
        <pubdate>2025-05-02T00:00:00Z</pubdate>
        <category>Perspective</category>
        <author>Steven Henikoff</author><author>Kami Ahmad</author>
        <description><![CDATA[Summary: The term “anaplasia” was coined in 1890 to describe chromosomal changes common to primordial cancer cells, but ever since the mechanisms whereby a cell becomes anaplastic has been the subject of much speculation. Recent results based on genomic and epigenomic profiles of cancer patient samples provide a glimpse into early events that lead to aneuploidy, the original defining feature of an anaplastic cell. We propose that the anaplastic cell is one in which RNA Polymerase II hypertranscribes S-phase-dependent histone genes, and the resulting histone excess facilitates DNA replication while competing for CENP-A, causing centromere breaks that initiate whole-arm aneuploidy.]]></description>
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