geneimprint : Hot off the Press

'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Sun, 03 May 2026 11:35:02 EDT Sun, 03 May 2026 11:35:02 EDT jirtle@radonc.duke.edu james001@jirtle.com Targeting Wnt/Î²-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell state diversity. Yang Y, Zhang X, Venkadakrishnan VB, Zou H, Zheng X, Guo S, Chen CZ, Borowsky AD, Corey E, Evans RM, Gao AC, Dall'Era MA, Zoubeidi A, Lara PN, Kung HJ, Chen X, Beltran H, Chen HW
J Clin Invest (May 2026)

PRC2/EZH2 inhibitors (PRC2i/EZH2i) are promising for the treatment of advanced cancers including metastatic prostate cancer. Here, we show that PRC2i/EZH2i alone or in combination with androgen receptor (AR) inhibitors induced diverse cell state programs (CSPs) (e.g., response to stress or IFN, MYC targets, stem cells, EMT lineage plasticity, and multiple developmental programs), which led to increased tumor cell invasion, metastasis, and resistance to other drugs, in addition to modest suppression of tumor growth. In contrast to the current perception, our comprehensive, integrated genomics and epigenomics profiling of patient-derived xenografts (PDXs) and clinical tumors revealed that PRC2/EZH2 suppressed CSP genes by maintaining chromatin bivalency. Hyperactive Wnt/Î²-catenin signaling and inhibitors of polycomb-repressive complex 2/enhancer of zeste homolog 2 (PRC2/EZH2) and the AR alter chromatin bivalency through antagonism of PRC2 and stimulation of MLL2/KMT2B in a feed-forward manner. The circadian rhythm regulator REV-ERBÎ± unexpectedly reprogrammed Î²-catenin in promoting bivalency resolution and CSP gene expression. Dual targeting of Wnt/Î²-catenin and EZH2 diminished diverse cell states by restoring bivalency and effectively blocked tumor growth. Our findings provide unexpected insights into chromatin bivalency and dysregulated circadian rhythms in the control of cell state diversity and identify alternative therapeutic strategies that target PRC2/EZH2 for advanced malignancies.]]> Wed, 31 Dec 1969 19:00:00 EST Exposome-induced dysregulation of glycemic homeostasis: Emerging biomarkers for diabetes risk and progression. Amalraj S, Karthick V, Thamarai R, Suganya M
Environ Pollut (May 2026)

Environmental exposures throughout life profoundly influence the development and progression of diabetes mellitus. The exposome, representing the totality of environmental exposures from conception to adulthood, interacts with genetic and metabolic pathways, leaving measurable signatures termed biomarkers. These biomarkers encompass indicators of exposure, biological effect, and susceptibility, providing mechanistic insights into glycemic regulation and disease progression. This review synthesizes current evidence on exposome-linked biomarkers in both Type 1 and Type 2 diabetes, highlighting chemical pollutants, dietary patterns, lifestyle factors, psychosocial stressors, and microbiome-derived metabolites as critical contributors to glycemic dysregulation. Advanced omics technologies, including metabolomics, proteomics, transcriptomics, and epigenomics, have facilitated the identification of these biomarkers, enabling a holistic understanding of environmental impacts on diabetes. Integrating exposomics with biomarker research offers potential for early detection, risk stratification, personalized interventions, and improved management of glycemic control. Knowledge gaps remain, particularly in longitudinal exposure mapping, causal inference, and translation into clinical practice. This review provides a comprehensive framework for understanding how environmental imprints shape metabolic health and identifies future directions for research in precision diabetes medicine.]]> Wed, 31 Dec 1969 19:00:00 EST Interactions between nutrition and the epigenome: how can it be harnessed for public health? Anastasopoulou M, Dereki I, Sgourou A, Lagoumintzis G
Future Sci OA (Dec 2026)

A substantial body of evidence shows that dietary habits influence gene expression and epigenetic processes, holding significant implications for public health policies. Epigenetic modifications are increasingly associated with metabolic state, disease risk, and biological aging. Translating mechanistic results into scalable, efficient nutritional epigenetics treatments is difficult.]]> Wed, 31 Dec 1969 19:00:00 EST Multi-ancestry transcriptome-wide association study reveals shared and population-specific genetic effects in Alzheimer disease. Sun X, Mews M, Wheeler NR, Benchek P, Gu T, Gomez L, Ray N, Reitz C, Naj AC, Below JE, Tosto G, Cornejo-Olivas M, Byrd GS, Feliciano-Astacio BE, Celis K, Rajabli F, Kunkle BW, Pericak-Vance MA, Haines JL, Griswold AJ, Bush WS
Am J Hum Genet (Apr 2026)

Alzheimer disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA sequencing (RNA-seq) and genotype data from NHW (n = 235), African American (AA; n = 224), and Hispanic (HISP; n = 292) Multi-Ancestry Genomics, Epigenomics, and Transcriptomics of Alzheimer's (MAGENTA) participants. Using sum of shared single effects (SuShiE) for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse-variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (false discovery rate [FDR] <0.05, posterior inclusion probability [PIP] >0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the genome-wide association study (GWAS) index SNP rs6733839 (r â 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.]]> Wed, 31 Dec 1969 19:00:00 EST Melatonin-enabled omics: understanding plant responses to single and combined abiotic stresses for climate-smart agriculture. Raza A, Li Y, Charagh S, Guo C, Zhao M, Hu Z
GM Crops Food (Dec 2026)

Climate change-driven single and combined abiotic stresses pose escalating threats to sustainable, climate-smart agriculture and global food security. Melatonin (MLT, a powerful plant biostimulant) has established noteworthy potential in improving stress tolerance by regulating diverse physiological, biochemical, and molecular responses. Therefore, this review delivers a comprehensive synopsis of MLT-enabled omics responses across genomics, transcriptomics, proteomics, metabolomics, miRNAomics, epigenomics, phenomics, ionomics, and microbiomics levels that collectively regulate plant adaptation to multiple abiotic stresses. We also highlight the crosstalk between these omics layers and the power of integrated multi-omics (panomics) approaches to harness the complex regulatory networks underlying MLT-enabled stress tolerance. Lastly, we argue for translating these omics insights into actionable strategies through advanced genetic engineering and synthetic biology platforms to develop MLT-enabled, stress-smart crop plants.]]> Wed, 31 Dec 1969 19:00:00 EST Multiâomics and their integration in psoriasis research (Review). Zhang H, Li D, Zhu L, Yan H, Yang L, Yang X, Zhou Y
Mol Med Rep (May 2026)

Psoriasis is a chronic, immuneâmediated skin disorder characterized by keratinocyte hyperproliferation, inflammatory infiltrates and systemic comorbidities. While genetic predisposition and immune dysregulation are established contributors, recent advancements in highâthroughput omics technologies have provided deeper insights into the molecular complexity of psoriasis. The present review synthesized findings from various omics layers, genomics, epigenomics, transcriptomics, proteomics, metabolomics and microbiomics, to elucidate their roles in psoriasis pathogenesis. Largeâscale genomeâwide association studies have identified both common and regionâspecific susceptibility loci. Epigenetic factors and transcription factors regulate psoriasisârelated genes by modulating chromatin accessibility, DNA methylation, nonâcoding RNAs and direct gene activation/inactivation, thereby reshaping the transcriptome. Genetic and epigenetic influences also drive significant alterations in the proteome and metabolome, both in the skin and plasma, shedding light on disease mechanisms and offering potential for biomarker discovery. While microbiome research in psoriasis remains in its early stages, shifts in skin and gut microbial communities have been observed, suggesting their involvement in disease pathogenesis. Together, the multiâlayered insights underscore the future potential of integrated systems approaches to unravel disease mechanisms and support the discovery of clinically actionable biomarkers and therapeutic targets, paving the way for more precise diagnosis and targeted therapeutic development in psoriasis.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). MÃ¼ller J, Laroche VT, Imm J, Weymouth L, Harvey J, Reijnders RA, Smith AR, van den Hove D, Lunnon K, Cavill R, Pishva E
Epigenetics (Dec 2026)

DNA methylation (DNAm) signatures are highly cell type-specific, yet most epigenome-wide association studies (EWAS) are performed on bulk tissue, potentially obscuring critical cell type-specific patterns. Existing computational tools for detecting cell type-specific DNAm changes are often limited by the accuracy of cell type deconvolution algorithms. Here, we introduce CEAM (Cell-type Enrichment Analysis for Methylation), a robust and interpretable framework for cell type enrichment analysis in DNA methylation data. CEAM applies over-representation analysis with cell type-specific CpG panels from Illumina EPIC arrays derived from nuclei-sorted cortical post-mortem brains from neurologically healthy aged individuals. The constructed CpG panels were systematically evaluated using both simulated datasets and published EWAS results from Alzheimer's disease, Lewy body disease, and multiple sclerosis. CEAM demonstrated resilience to shifts in cell type composition, a common confounder in EWAS, and remained robust across a wide range of differentially methylated positions, when upstream modeling of cell type composition was modeled with sufficient accuracy. Application to existing EWAS findings generated in neurodegenerative diseases revealed enrichment patterns concordant with established disease biology, confirming CEAM's biological relevance. The workflow is publicly available as an interactive Shiny app (https://um-dementia-systems-biology.shinyapps.io/CEAM/) enabling rapid, interpretable analysis of cell type-specific DNAm changes from bulk EWAS.]]> Wed, 31 Dec 1969 19:00:00 EST A genomic and epigenomic view of human centromeres. Jaggi KE, Hoyt SJ, O'Neill RJ, Sullivan BA
Nat Rev Genet (May 2026)

Human centromeres are large, complex chromosomal loci that serve as the foundation for kinetochore assembly, contribute to chromosome architecture and sister chromatid cohesion, and participate in chromosome separation during cell division. Encoded by thousands to millions of base pairs of repetitive DNA, these regions were previously represented as gaps in the human genome assembly due to limitations in sequencing technologies and computational tools that could accurately distinguish and anchor the highly similar repeats within a linear genome assembly. Substantial advances in long-read sequencing over the past 5 years have permitted these large human centromere regions to be spanned, revealing new genomic and epigenomic information and the structural organization of these essential regions. Here, we review these discoveries and discuss knowledge gaps that have been filled and emerging functional questions.]]> Wed, 31 Dec 1969 19:00:00 EST TiSMeD: A tissue-specific methylation and expression database for biomarker and translational applications. Cheng J, Lin Z, Wu L, Li Q, Yin H, Wang H, Chen H, Chen X, Ji ZL
Mol Ther Nucleic Acids (Jun 2026)

Tissue-specific methylation sites (TSMs) are important epigenetic features associated with gene regulation, tissue development, and disease pathogenesis. However, the lack of comprehensive and reliable resources for TSMs restricts advancements in epigenetic and translational research. We present TiSMeD (http://www.bio-add.org/TiSMeD/), a multi-omics database integrating 6,782 DNA methylation, 16,894 transcriptome, and 241 proteome profiles across 48 normal human tissues. Using a scoring framework based on SPM and Tscore, we identified 67,427 high-confidence TSMs, 4,607 tissue-specific genes, and 2,833 tissue-specific proteins, along with over 11 million housekeeping methylation sites. TiSMeD enables interactive exploration and data retrieval, supporting biomarker discovery and disease research. We demonstrate its utility in tracing the tissue-of-origin of cell-free DNA (cfDNA), prioritizing 1,849 cancer biomarkers from The Cancer Genome Atlas (TCGA), and constructing a multi-cancer tracing and diagnostic model achieving 95.7% accuracy. TiSMeD serves as a robust, user-friendly platform integrating multi-omics data to advance epigenetic research and biomarker translation.]]> Wed, 31 Dec 1969 19:00:00 EST Global analyses of genomic and epigenomic influences on gene expression reveal as a major regulator of cardiac gene expression in response to catecholamine challenge during heart failure. Lahue C, Ravindran S, Dalal A, Avetisyan R, Rau CD
Epigenetics (Dec 2026)

Heart failure arises from maladaptive remodelling driven by genetic and epigenetic networks. Using a systems genetics framework, we mapped how DNA variants and CpG methylation shape cardiac transcriptomes during beta adrenergic stress in the Hybrid Mouse Diversity Panel, a cohort of over 100 fully inbred mouse strains. Expression QTLs (eQTLs), methylation QTLs (mQTLs) and methylation-driven eQTLs (emQTLs) were generated from over 13k expressed genes and 200k hypervariable CpGs in left ventricles. We discovered hundreds of regulatory 'hotspots' that control large portions of the genome, including several that regulate over 10% of the transcriptome and/or methylome. Approximately 16% of these hotspots overlapped with prior GWAS or EWAS signals. We focus on a hotspot on chromosome 12 and identify the serpine peptidase inhibitor , as the most likely driver gene in this hotspot. Experimental knockdown of in neonatal rat ventricular cardiomyocytes blunted hypertrophy induced by a variety of hypertrophic signals, while altering predicted target expression and modulating the activity of and . Together, these findings position as a major regulator of stress-responsive cardiac gene programs, highlighting how integration of genetic and epigenetic signals can pinpoint key drivers of heart failure.]]> Wed, 31 Dec 1969 19:00:00 EST FINE-EM-seq: a rapid isothermal amplification method enabling comprehensive methylome profiling of zebrafish early embryos. Ding C, Zhang Q, Wang J, Xu Y, Huang T, Du Y, Zhang J, Zhou X, Liu Y, Hu Z
Cell Insight (Jun 2026)

DNA methylation plays a crucial role in development and disease. Bisulfite-free methods such as enzymatic methyl sequencing (EM-seq) offer gentle approaches for whole-genome analysis, but they typically depend on PCR-based library amplification, which distorts coverage and methylation quantification. Here, we introduce FINE (Fast Isothermal amplification via Nicking Enzyme), a robust isothermal amplification strategy that leverages a nicking enzyme-assisted strand displacement reaction and can amplify methylation libraries from sub-nanogram inputs in 20 min. FINE-EM-seq increases library efficiency and coverage uniformity compared to PCR-based approaches, minimizing amplification bias and improving methylation calling accuracy. Applied to zebrafish embryos at four early developmental stages, FINE-EM-seq characterized stage-associated methylation dynamics through blastulation and early gastrulation. Furthermore, our analysis revealed blastulation-associated differentially methylated regions (DMRs) overlapping with AT-rich regions that were previously under-covered. These results illustrate that FINE-EM-seq is a rapid, robust solution for low-input whole-genome methylation sequencing with broad utility in developmental biology and clinical epigenomics.]]> Wed, 31 Dec 1969 19:00:00 EST A Framework for Advancing Mechanistic Neurobehavioral Biomarkers in Psychiatry. Lee K, Ji JL, Helmer M, Murray JD, Krystal JH, Anticevic A
Biol Psychiatry (May 2026)

Neuropsychiatry has yet to surmount the fundamental challenge of mapping behavioral pathology to its underlying neural pathology. This gap limits the development of treatments for specific circuit pathologies, despite the great potential of neuroimaging measures. We show that the field may be moving toward refining limited statistical frameworks, while clinically translatable solutions could emerge with broader considerations. We posit that the failure to operate within a formalism that defines falsifiable parameters might have hindered progress. Here, we propose a provisional formalism with the intention of bringing elements into focus that seem necessary to advance the development of precision treatments in psychiatry. Specifically, we propose that this formalism should consider 3 defining axes: 1) type of mechanism, 2) severity of mechanism, and 3) time. These 3 axes define a 3-dimensional dynamic mechanism complexity space (MCS). In turn, we posit that at any point in this MCS, there are embedded neurobehavioral subspaces or geometries for neural-to-symptom variation, which themselves are multidimensional and dynamic. This formalism provides for the mapping of the MCS to a neurobehavioral subspace. Furthermore, we articulate how this formalism accommodates integration of spectra from genetics and systems biology (transcriptomics, epigenomics, etc.) to neural mechanisms, symptom variance, and ultimately taxa of mental illness (i.e., categories). Finally, we argue that this formalism creates an opportunity to evaluate different types of treatment development that map onto dynamically evolving mechanisms of illness that are likely a hallmark feature of neuropsychiatric illness.]]> Wed, 31 Dec 1969 19:00:00 EST T-ChroNet: Time-aware chromatin network reconstruction to detect dynamic regulatory programs in longitudinal epigenetic dataset. Di Giovenale S, Lischio O, Cortile C, Corleone G, Fanciulli M, Bonchi F, Barozzi I
NAR Genom Bioinform (Jun 2026)

Networks are widely applied to investigate relationships among individual components of complex biological systems. Recent application of biological networks, such as gene co-expression networks and gene regulatory networks, has been instrumental to define principles of transcriptional modulation in development and disease. However, computational methods that can embed the activity of -regulatory elements (CRE) into a network are still limited. Capturing temporal CRE activity within a network could help reveal regulatory programs involved in cell fate commitment and disease development. To address this, we present T-ChroNet (Time-aware Chromatin Network), a network-based method that models CRE as nodes and their temporal co-accessibility as edges. Through the detection of CRE sharing similar accessibility patterns over time, T-ChroNet allows the inference of putative upstream regulators and downstream biological pathways. We applied T-ChroNet to temporally-resolved CRE datasets, from both human and mouse, including chromatin accessibility (ATAC-seq) and histone post-translational modifications (H3K27ac ChIP-seq). T-ChroNet successfully recovered known regulators and enriched pathways for both modalities and species, while also uncovering novel putative factors and mechanisms regulating cell identity, organ development and disease progression.]]> Wed, 31 Dec 1969 19:00:00 EST Impact of vitamin D deficiency on defective endometrial decidualization and the repressive role of vitamin D receptor (VDR) in the epigenomic network. Yi M, Montague Redecke SG, Wang T, Bell-Hensley A, Li S, Massri AJ, Jukic AMZ, DeMayo FJ
Pharmacol Res (May 2026)

Identifying the factors that regulate female reproduction is crucial to understanding how the environment affects female reproductive health. The vitamin D receptor (VDR) and its ligands (primarily 1,25(OH)D) have a recognized role in calcium homeostasis; however, their broader impact on female reproduction remains underexplored. We demonstrate that the VDR and its ligands are involved in the hormonal induction of uterine decidualization. Mice fed a vitamin D-deficient diet displayed an impaired hormonally induced decidual response. In a human telomerase reverse transcriptase-immortalized human endometrial stromal cell line (T-HESC), VDR decreased during in vitro decidualization. Small interfering RNA (siRNA) knockdown of VDR in T-HESC enhanced in vitro decidualization, while overexpression of VDR inhibited it. Chromatin accessibility and histone modification analyses revealed that VDR functions as a chromatin regulator, restricting accessibility and repressing transcription in specific genomic regions. Transcriptomic analyses confirmed that VDR broadly modulates gene expression, with most ligand-mediated effects occurring through the VDR. These findings identify VDR as a key regulator of transcriptional and chromatin landscapes in human endometrial stromal cells, offering novel insights into vitamin D signaling in reproduction. This study highlights the potential of targeting vitamin D pathways to treat uterine disorders associated with impaired decidualization and reduced fertility.]]> Wed, 31 Dec 1969 19:00:00 EST H19 lncRNA in programming prenatal development and DOHaD due to maternal obesity. Islam S, Du M
Life Sci (Jun 2026)

Maternal obesity is a major global health challenge worldwide, significantly increasing the risk of pregnancy complications and long-term metabolic disorders in offspring. Maternal obesity, including associated gestational diabetes, induces epigenetic modifications that can reprogram fetal development and predispose children to lifelong health issues. Long non-coding RNA (lncRNA) H19, one of the first and most extensively studied lncRNAs, plays a pivotal role in developmental programming by regulating gene imprinting, microRNA processing, protein stabilization, and signaling pathways critical for growth and metabolism. Dysregulation of H19 expression under maternal obesity alters the H19/Igf2 (insulin-like growth factor 2) imprinting axis, disrupts skeletal muscle development, and modifies osteogenic and neurogenic pathways, thereby contributing to systemic insulin resistance, metabolic dysfunction, and neuro-disorder in offspring. This review highlights how maternal obesity reprograms offspring health through H19-mediated epigenetic and post-transcriptional regulation, emphasizing its role in the developmental origins of health and disease framework. Understanding the role of H19 offers valuable opportunities to develop targeted interventions that may reduce the transgenerational effects of obesity.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic analyses suggest different pathways during pregnancy for development of type 1 diabetes in children with high versus low-neutral human leukocyte antigen-risk. Alipoor SD, Ahrens A, Ãkesson J, Hillerton T, Gustafsson M, Lerm M, Ludvigsson J
J Intern Med (May 2026)

The development of Type 1 diabetes (T1D) is shaped by genetic predisposition and epigenetic regulation. Human leukocyte antigen (HLA) risk alleles are major genetic determinants, but the epigenetic landscape in relation to disease onset remains unclear. Early-life epigenetic modifications may reveal how environmental and epigenetic factors interact in T1D pathogenesis.]]> Wed, 31 Dec 1969 19:00:00 EST Long noncoding RNA H19 in liver development and disease. Montoya-Durango DE, Gobejishvili L
Cell Signal (Jun 2026)

Liver disease is a global health problem responsible for more than two million deaths annually. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are major contributors to chronic liver disease-related morbidity and mortality. Factors like diet and alcohol consumption have become key drivers of liver pathologies including steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma. To date very few treatments are available, hence there is a critical need for the development of novel therapies to slow down the development/progression of liver damage. The long non-coding RNA H19 gene, H19, is an imprinted gene normally expressed from the maternally inherited chromosome and epigenetically silenced in the paternal chromosome. At the embryo stage H19 controls genome-wide methylation, directs the methylation of the imprinted gene network, and regulates organ size. In the livers of neonates, H19 is important for organ maturation but remains silent in the mature organ. H19 re-expression in the adult liver drives de novo lipogenesis and fibrosis and maintains a proliferative state in tumor cells. The complexity of H19 functions in the liver is reflected in its interaction and regulation of a growing number of proteins, and coding and non-coding RNAs involved in metabolism, pro-fibrotic gene networks, cell cycle progression, and chromatin regulation. This review summarizes the findings related to the role of H19 in liver development and in diseases such as fatty liver, fibrosis, and hepatocellular carcinoma.]]> Wed, 31 Dec 1969 19:00:00 EST Epigenetic orchestration of cancer-immune dynamics: mechanisms, technologies, and clinical advancements. Lu Y, Ma S, Chan YT, Wu Y, Feng Y, Wang N
J Adv Res (May 2026)

Epigenetic dysregulation plays a pivotal role in cancer immune evasion by orchestrating tumour antigen silencing, immune cell dysfunction, and the formation of an immunosuppressive microenvironment. By disrupting successive phases of the cancer-immunity cycle-from antigen presentation to T cell exhaustion-these aberrations facilitate immune escape and tumour progression, highlighting the need for targeted epigenetic intervention.]]> Wed, 31 Dec 1969 19:00:00 EST Microglia in human models of development and disease: are we prioritising model 'success' over biological truth? Barresi M, Ravi Prasad R, Quigley A, Gressens P, Tolcos M, Fleiss B
Neuroscience (May 2026)

MeSH terms: Microglia/growth & development; Induced Pluripotent Stem Cells /differentiation; Organoids/physiology; Epigenomics; Cell Lineage.]]> Wed, 31 Dec 1969 19:00:00 EST Seeing and Feeling DNA Methylation: Single-Molecule Biophysics Meets Machine Learning. Agrawal T, Pal S, Rakshit T
Nano Lett (Apr 2026)

DNA methylation at 5-methylcytosine (5mC) is crucial for embryonic development and cellular function, while aberrant patterns strongly drive disease onset and progression. Its reversible nature offers substantial therapeutic potential, emphasizing the need for precise, context-specific genome wide 5mC mapping. Conventional techniques such as bisulfite sequencing and ensemble biosensor assays are hindered by DNA degradation, amplification bias, high cost, and inability to resolve single-molecule structural and mechanical effects of methylation. This review examines advances in single-molecule biophysical methods (nanopore sensing, smFRET, optical/magnetic tweezers, and AFM) that provide direct, label-free/minimally invasive 5mC detection, along with quantitative insights into DNA conformation, mechanics, and protein-DNA interactions. These techniques complement traditional methylome mapping by linking genomic localization to molecular mechanisms. Emerging machine-learning approaches are revolutionizing analysis, particularly in nanopore sensing, while promising applications in smFRET, tweezers, and AFM address throughput and reproducibility challenges. Their convergence promises scalable, high-resolution epigenetic profiling, advancing precision epigenomics toward clinical application.]]> Wed, 31 Dec 1969 19:00:00 EST