'; ?> 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 Mon, 08 Jun 2026 14:35:08 EDT Mon, 08 Jun 2026 14:35:08 EDT jirtle@radonc.duke.edu james001@jirtle.com Epigenetic Regulation of Nephrogenesis: From Waddington's Landscape to Adult Disease. Tortelote GG, El-Dahr SS
Am J Physiol Renal Physiol (Jun 2026)

The establishment of lifelong nephron endowment depends on the tightly coordinated regulation of nephron progenitor cell (NPC) self-renewal, lineage specification, and differentiation during kidney development. Conrad H. Waddington's developmental landscape provides a powerful conceptual framework for understanding how NPCs navigate sequential fate decisions toward mature renal epithelial identities. Within this paradigm, the topology of the landscape is actively shaped by epigenetic mechanisms, including DNA methylation, histone post-translational modifications, non-coding RNA-mediated gene regulation, and higher-order chromatin organization, which collectively control the timing, location, duration, and strength of gene expression programs that direct nephrogenesis. Under normal conditions, these epigenetic programs preserve progenitor competence while progressively stabilizing lineage commitment and nephron patterning. When disrupted, however, they impair progenitor plasticity, accelerate NPC pool depletion, and ultimately reduce nephron number. Such maladaptive epigenetic reprogramming establishes a mechanistic link between adverse intrauterine environments and lifelong susceptibility to hypertension and chronic kidney disease. In this review, we revisit Waddington's landscape in the context of renal development and integrate emerging insights from developmental biology, cell metabolism, and epigenomics to examine how early-life environmental perturbations durably reshape the nephrogenic program and increase the risk of adult-onset kidney disease.]]> Wed, 31 Dec 1969 19:00:00 EST Arsenic exposure at birth, socioeconomic status, and epigenetic aging among adults in northern Chile. Kwon D, Bozack AK, Ferreccio C, McCormick N, Steinmaus CM, de la Rosa R, Cardenas A
Environ Res (Jun 2026)

Arsenic exposure remains a major global health concern, and early-life exposure has been linked to cancer, cardiovascular disease, and diabetes. Epigenetic biomarkers of aging may capture long-term effects of arsenic, yet whether exposure during sensitive developmental windows leaves detectable epigenetic signatures decades later remains unclear. Socioeconomic status (SES) may modify these relationships, yet its role as a modifier has not been examined.]]> 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 Epigenetic reprogramming of tissue-resident memory T cells in chronic inflammatory disorders and implications for targeted therapies. Ling C, Isleem HF, Tejani GG
Epigenomics (Jun 2026)

Tissue-resident memory T (TRM) cells play a role in causing long-term tissue injury in chronic inflammatory diseases via pathological epigenetic reprogramming. Nevertheless, the epigenetic processes that cause this malfunction have not been well defined.]]> Wed, 31 Dec 1969 19:00:00 EST Advanced deep learning strategies in nanopore RNA sequencing. Ling C, Lebeau B, Keong KC, Fullwood M
RNA Biol (Dec 2026)

The epitranscriptome comprises chemical modifications found on RNA molecules that play essential roles in co- and post-transcriptional gene regulation. Dysregulation of these modifications has been implicated in various diseases, fuelling interest in evaluating them as emerging biomarkers and therapeutic targets. Nanopore direct RNA sequencing provides a powerful platform for profiling diverse RNA modifications at single-molecule resolution, but the complexity of the signals requires advanced computational approaches for interpretation. Artificial intelligence, particularly deep learning (DL), has become central to this effort. While classical DL architectures such as convolutional and recurrent neural networks have been widely applied, more recent approaches employ specialized learning frameworks and ensemble strategies to address challenges of data scarcity, noise, and biological variability while providing higher resolution output. In this review, we summarize these developments and highlight future multidisciplinary opportunities at the intersection of artificial intelligence and biology for characterizing the epitranscriptome obtained with direct RNA nanopore sequencing.]]> Wed, 31 Dec 1969 19:00:00 EST Charting the human-specific properties of gene expression networks in the infant prefrontal cortex. Klavert J, Radjabzadeh D, Gonzalez Sanchez E, Castelijns B, Timpanaro IS, Boers J, Fabro F, Vroeg In de Wei G, Bindels E, Kondova I, Gribnau J, Creyghton MP
Sci Adv (Jun 2026)

Human infancy is characterized by protracted brain development coinciding with sensitive periods of extensive synaptic remodeling. Whether this is supported by human infant-specific transcriptional programs is unknown as comparative material in closely related primate species was unavailable. Here, we analyze rare newborn chimpanzee and age-matched human and rhesus macaque brain samples using single-cell transcriptomics and epigenomics. We identify a human infant-specific transcriptional program in immature oligodendrocytes that is overrepresented in autism risk genes and patient gene expression changes. Furthermore, a human infant-specific transcriptional program in the neural lineage is overrepresented in Parkinson's disease risk genes and patient gene expression changes. Both of these programs are part of a core transcriptional network that contains human-specific sequence changes in regulatory DNA and lacks cell lineage specificity. Our study provides insights into the stage-specific properties of human evolution during early infancy and sheds light on the human-specific propensities to neural disease.]]> 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 Methods toward Single-Cell Total-Analysis. Zhang Q, Liao W, Lin L, Li XJ, Lin J, Song Y, Hou Y, Lin JM
Chem Rev (Jun 2026)

Single-cell total-analysis aims to bridge the gap between cellular molecular makeup and functional phenotype, deciphering how genomic, transcriptomic, proteomic, and metabolic networks orchestrate phenotypic outcomes. Despite rapid omics advances, a critical disconnect persists: nucleic acid-based analyses (genomics, epigenomics, transcriptomics) are mature, while proteomic/metabolomic profiling is incomplete, and comprehensive phenomics (the direct readout of cellular function) lags due to dynamic cellular complexity. This raises a core question: how to transcend isolated molecular layers to capture the ″molecular-phenotypic correlation″ in single cells? Multimodal integration progresses but is constrained by technical incompatibilities, throughput-depth trade-offs, and poor temporal resolution. This review examines advances in five core omics domains, identifies bottlenecks, analyzes multiomics coanalysis strategies, and outlines a roadmap for true single-cell total-analysis, emphasizing breakthrough approaches to unify molecular and phenotypic landscapes. We propose that true single-cell total-analysis is defined not by the accumulation of multiomic molecular layers, but by the direct establishment of phenotype-component correlations within the same individual cell.]]> Wed, 31 Dec 1969 19:00:00 EST A cell type enrichment analysis tool for brain DNA methylation data (CEAM). Müller 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 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 Epigenetic research methods and animal models for intervertebral disc degeneration (Review). Cui X, Zeng L, Zhang W, Xi L, Wang R, Jia D, Safa , Feng H, Jia H
Mol Med Rep (Jul 2026)

Intervertebral disc degeneration (IVDD) is increasingly recognized as a systemic collapse of the epigenetic regulatory network, driven by cellular senescence and environmental stressors. The present review provides an overview of the epigenetic regulatory mechanisms governing IVDD, focusing on the dynamic interplay between DNA methylation, histone modifications, N6‑methyladenosine RNA methylation and the non‑coding RNA regulatory triad (microRNAs, long non‑coding RNAs and circular RNAs). The present study evaluates advanced research methodologies (ranging from site‑specific methylation typing and transposase accessible chromatin sequencing to single‑cell multi‑omics and artificial intelligence‑driven predictive modeling) that resolve the spatial and cellular heterogeneities of the degenerating disc niche. Furthermore, the translational constraints of current animal models were critically assessed, advocating for a strategic shift from acute needle‑puncture insults to physiologically relevant aging and genetically engineered progeroid models to better recapitulate human 'epigenetic drift'. Finally, the therapeutic potential of targeted epigenetic editing via CRISPR/dCas9 systems and the development of stimuli‑responsive nanocarriers for precision delivery are highlighted. By bridging methodological innovation with robust model selection, the present review offers a roadmap for transitioning molecular insights into clinical regenerative therapies for spinal health.]]> Wed, 31 Dec 1969 19:00:00 EST Omics-driven strategies for identifying biomarkers in Alzheimer's disease. Khan Y, Rekha A, Ballal S, Maharana L, Maqbool M, Goyal K, Mishra R, Uniyal P, Alam P, Aljarba TM, Gupta G, Hussain MS
Metab Brain Dis (Jun 2026)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options, mainly due to late diagnosis and partial understanding of its molecular aspects. Traditional biomarker discovery approaches have significantly contributed to AD diagnostics but suffer from limitations. The advent of omics technologies (genomics, epigenomics, transcriptomics, proteomics, and metabolomics) has revolutionized the search for novel biomarkers by enabling comprehensive molecular profiling. Genomic studies have identified risk-associated variants such as APOE4, while epigenomic alterations, including DNA methylation alterations, offer insight into gene regulation in AD. Transcriptomic analyses, particularly single-cell and spatial transcriptomics, have uncovered molecular pathways linked to neuroinflammation and synaptic dysfunction. Proteomic advancements, including mass spectrometry and extracellular vesicle profiling, have identified potential blood- and CSF-based biomarkers for early-stage detection. Metabolomic and lipidomic studies indicate that cerebral glucose hypometabolism, insulin resistance, mitochondrial damage, redox imbalance, and disrupted lipid homeostasis are centra contributors to AD pathogenesis rather than secondary considerations of the disease. These metabolic dysfunctions may precede overt neurodegeneration and influence amyloid processing, tau phosphorylation, neuroinflammatory activation, and synaptic loss, thereby generating clinically informative biomarker signatures in blood and cerebrospinal fluid. Within this metabolism-centered paradigm, integrative multi-omics approaches are particularly valuable because they not only enhance biomarker specificity, but also connect molecular signatures with bioenergetic and immune-mediated mechanisms of disease. Accordingly, integrative multi-omics approaches improve biomarker specificity and predictive power, thereby supporting the development of precision medicine and targeted therapeutic interventions. Nevertheless, important challenges remain, including data integration, reproducibility, and clinical translation.]]> Wed, 31 Dec 1969 19:00:00 EST Cholangiocyte biology in primary sclerosing cholangitis and other cholangiopathies: pathogenesis, clinical insights, and experimental tools. Jalan-Sakrikar N, Anwar AA, Ali A, Nasser-Ghodsi N, Felzen A, Huebert RC, LaRusso NF, O'Hara SP
Physiol Rev (Jul 2026)

Cholangiocytes are specialized epithelial cells that line the intrahepatic and extrahepatic biliary tree and play a critical role in bile modification, liver homeostasis, and response to injury. Cholangiocytes exhibit notable heterogeneity and plasticity, and their dysfunction is central to a spectrum of diseases targeting the bile ducts, collectively called cholangiopathies. These disorders include genetic, infectious, immune-mediated, and malignant diseases, with primary sclerosing cholangitis (PSC) representing one of the most complex and enigmatic of these disorders. PSC is a progressive, fibro-inflammatory disease of the bile ducts that is closely linked to inflammatory bowel disease, carries a heightened risk of cancer, and lacks any approved therapies. This review explores the biology of cholangiocytes, including their development, functional plasticity, and roles in secretion, absorption, and cellular signaling. We provide a detailed examination of cholangiopathies, particularly PSC, a complex cholangiopathy characterized by a paradoxical state of cholangiocyte senescence and hyperproliferation. We describe how immune cell dysfunction, the gut microbiome, genetic predispositions, and environmental factors converge to mediate PSC pathogenesis. We revisit the foundational technologies that empowered early discoveries and shaped the field as we know it today. We also explore how newer techniques such as organoid cultures, single-cell transcriptomics, epigenomics, and spatialomics have transformed our modern understanding of biliary pathophysiology. Finally, we provide an overview of existing rodent models of cholangiopathies and discuss their relevance to human disease. PSC remains therapeutically unaddressed, and thus ongoing multidisciplinary efforts are essential to developing targeted interventions. This review serves as a comprehensive resource for researchers and clinicians navigating the rapidly evolving landscape of cholangiocyte-centered liver disease research.]]> Wed, 31 Dec 1969 19:00:00 EST Single-cell mapping of regulatory DNA-protein interactions. Chi WY, Yoon SH, Goksel E, Mekerishvili L, Pelt J, Lin Y, Prieto T, Zinno J, Ganesan S, Potenski C, Izzo F, Landau DA, Raimondi I
Cell (Jun 2026)

Gene expression is controlled by transcription factors (TFs), whose genome binding is shaped by chromatin accessibility and histone modifications, yet mapping these interactions, particularly those with weak affinity or a transient nature, in single cells remains technically challenging. To address this gap, we developed docking and deamination followed by sequencing (D&D-seq), a single-cell immuno-tethering technology for profiling DNA-protein interactions. D&D-seq couples an antibody-binding nanobody to a cytosine base editor, a combination that enables detection of weak or transient factor binding through targeted cytosine-to-uracil editing at protein-bound genomic sites. This approach is compatible with standard single-cell multi-omic workflows and therefore allows integrated analyses of gene regulation. Using assay for transposase-accessible chromatin using sequencing (ATAC-seq) and single-cell ATAC-seq (scATAC-seq), we assessed chromatin accessibility as a functional readout of TF activity, and by coupling D&D-seq with whole-genome sequencing, we captured CTCF binding in both active and inactive chromatin compartments.]]> Wed, 31 Dec 1969 19:00:00 EST Beyond Weight: Systems Biology and Precision Medicine Redefine Obesity as a Multidimensional Disease. Liu Y, Yang Y, Zhu L, Peng W
Diabetes Obes Metab (Jul 2026)

Traditional weight-centered models do not fully capture the biological complexity of obesity. Systems biology offers a new framework by integrating molecular, cellular, clinical, and environmental information to reframe obesity as a heterogeneous, multidimensional disease.]]> 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 (Jun 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 ≈ 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 The transformative role of single-cell analysis in multifactorial disorders research. Wang CY, Ko CC, Kumar S, Xuan DTM, Lin HR, Lee YK, Nguyen NUN, Yang PM, Solomon DD
Methods (Jul 2026)

Multifactorial inherited disorders (MIDs) arise from complex interactions between polygenic risk and environmental exposures, presenting major challenges for mechanistic discovery, patient stratification, and targeted therapy development. While traditional approaches like genome-wide association studies (GWAS) and bulk omics profiling have identified broad associations, they often struggle to resolve the cellular context in which these interactions drive pathogenesis.Emergingsingle-cell technologies now offer unprecedented resolution to dissect tissue heterogeneity, define rare or transient disease-relevant cell states, and map dynamic trajectories across tissues and disease stages. This reviewprovides a comprehensive synthesis ofcurrent single-cell methodologies including transcriptomic, epigenomic, proteomic, and spatial techniques and their application to MID research. We explore how these toolsare revealingcell-type-specific regulatory circuits,contextualizingthe functional impact of inherited risk variants, andelucidatingcellular responses to environmental perturbations.We propose thatintegrating single-cell multi-omics data is critical for illuminating the mechanistic basis of complex traits and for advancing biomarker discovery. However, significant challenges remain, including technical variability, limited cohort scalability, difficulties in multi-modal data integration, and a lack of standardized analytical workflows for polygenic diseases. Overcoming these barriers will require harmonized study designs, robust computational frameworks, and the incorporation of longitudinal and environmental exposure data.Ultimately, we conclude thatsingle-cell analysis is poised to transform MID research, offering a powerful new paradigm for mechanistic insight, therapeutic innovation, and the realization of precision medicine.]]> Wed, 31 Dec 1969 19:00:00 EST Pathogen-triggered m⁶A epitranscriptomic reprogramming is linked to host defense responses in the Piper nigrum-Phytophthora capsici pathosystem. Salim S, Revikumar Sunitha L, Eppurath Vasudevan S
Plant Cell Rep (Jun 2026)

Pathogen infection by the oomycete Phytophthora capsici induces dynamic m⁶A epitranscriptomic remodeling in black pepper, linking m⁶A-associated regulation with defense-related pathways including phenylpropanoid metabolism, reactive oxygen species (ROS) responses, and lignification. This study provides evidence for epitranscriptomic regulation of host defense in the Piper nigrum-Phytophthora capsici pathosystem. Foot rot (quick wilt) caused by the oomycete Phytophthora capsici is a major constraint to the cultivation of Piper nigrum L. (black pepper). Although N⁶-methyladenosine (m⁶A) RNA modification has emerged as an important component of plant stress responses, its role in black pepper-P. capsici interactions remains unclear. Here, we investigated the dynamics and potential functional relevance of m⁶A during pathogen infection. Dot blot analysis and transcriptome-wide profiling (MeRIP-seq) indicated increased m⁶A enrichment in infected leaves compared with healthy controls. Spatiotemporal analyses further revealed enhanced m⁶A-associated signals at local infection sites as well as in distal tissues, suggesting infection-associated changes in tissues beyond the primary infection site. Pharmacological perturbation using 3-deazaneplanocin A (DZnep) and meclofenamic acid (MA) resulted in increased disease severity and enhanced pathogen colonization, suggesting that methylation-related processes may contribute to host resistance. However, given the pleiotropic effects of these inhibitors, the observed responses are interpreted as indirect evidence of methylation-associated regulation. Functional enrichment analysis showed that m⁶A-associated transcripts are linked to key defense-related processes, including phenylpropanoid metabolism, lignification, and reactive oxygen species (ROS)-mediated responses. Together, these findings suggest that m⁶A methylation may represent a dynamic regulatory layer in black pepper immunity and provide a foundation for future studies on epitranscriptomic regulation of plant defense during oomycete infection.]]> 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 m6A RNA Methylation Mediates the Immune Gene Regulatory Mechanism in Against Infection. Cao M, Wu R, Liu C, Li C
J Agric Food Chem (Jun 2026)

is a major pathogen in mariculture. The role of epitranscriptomic regulation in fish mucosal immunity remains unclear. We employed MeRIP-seq and RNA-seq to investigate m6A modifications in during infection. We identified 6523-7361 differential m6A peaks, with a shift toward 3'UTRs. Transcriptome analysis revealed that 1279 DEGs were enriched in complement and cytokine pathways while inflammatory mediators were suppressed at 6 hpi. At 24 hpi, 579 DEGs sustained acute-phase responses and pathogen recognition. Notably, 77 continuously upregulated and 145 downregulated immune genes were identified. Temporal m6A dynamics indicated suppressed early methylation, while induction facilitated late demethylation. Region-specific m6A regulation was observed that 5'UTR demethylation activated , while 3'UTR methylation suppressed Functional analysis suggests m6A methylation suppresses inflammation, while demethylation enhances pathogen clearance via complement and antigen presentation pathways. This study reveals epitranscriptomic regulation in teleost immunity and suggests targets for disease-resistant aquaculture.]]> Wed, 31 Dec 1969 19:00:00 EST