To investigate epigenetic and transcriptional alterations in children with Wiedemann-Steiner syndrome (WDSTS) due to variants of KMT2A gene using genome-wide DNA methylation array and RNA sequencing (RNA-seq), and identify the key pathways and candidate genes. A retrospective study was carried out for 16 children with WDSTS and 10 healthy controls who visited Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine between November 2016 and December 2024. Peripheral blood samples were collected. Genomic DNA and total RNA were extracted using commercially made kits. Genome-wide DNA methylation profiling was conducted to identify differentially methylated positions (DMPs) and annotated genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RNA-seq was performed to identify differentially expressed genes (DEGs) and conduct GO/KEGG functional annotation. Methylation and expression data were integrated to identify overlapping genes showing significant changes at both levels, followed by GO, KEGG and gene-pathway network analyses. This study was approved by the Ethics Committee of the hospital (Ethics No.: GKLW-A-2024-006-01). A total of 2 652 DMPs corresponding to 1 262 genes were identified, which included 833 hypermethylated genes (66%) and 429 hypomethylated genes (34%). Hypermethylated genes were mainly enriched for functions related to cell junctions, while hypomethylated genes were significantly involved in nervous system development and morphogenesis. RNA-seq identified 2 627 DEGs, including 765 up-regulated genes (29%) and 1 862 down-regulated genes (71%). Up-regulated genes were mainly associated with immune-related processes, and down-regulated genes were mainly related to substance transport. Integrative analysis identified 93 overlapping genes with significant changes in both methylation and expression. And these genes were enriched in extracellular matrix-related processes, calcium ion binding, neurodevelopment, and cell adhesion. Key candidate genes, including LAMB1, LAMB2 and NID1, were further prioritized. Integrated analysis of DNA methylation and transcriptome data reveals WDSTS-related epigenetic-transcriptional alterations and provides clues for exploring disease mechanisms and optimizing diagnostic strategies.

Novel mechanisms and emerging therapeutic strategies in vascular calcification.

Elimination of carryover contamination for DNA methylation analysis based on isothermal amplification and lateral flow assay.

Anthocyanin-mediated epigenetic modifications: a new perspective in health promoting and disease prevention.

DNA methylation as a biomarker of salinity and contaminant stress in mangrove crab Ucides occidentalis.

UVB induces DNA hypomethylation and cell activation in CD4+ T cells of systemic lupus erythematosus via miR-410 regulating GADD45A.

Low-dose aspirin (LDA) is an intervention recommended to prevent the development of hypertensive disorders of pregnancy (HDP) in high-risk pregnancies. Maternal conditions such as HDP have been associated with cord blood epigenetic changes including those related to cardiovascular processes; however, it is unclear whether maternal aspirin therapy may impact neonatal epigenetics in otherwise healthy high-risk pregnancy. This study aimed to determine if maternal LDA exposure in utero leads to altered DNA methylation in umbilical cord blood cells in term neonates compared with controls not exposed to aspirin, and to identify if these methylation changes alter key pathways in the development of chronic disease. Umbilical cord blood was collected from 10 neonates without LDA exposure and 13 neonates with LDA exposure in utero. Patients with hypertensive disorders of pregnancy, COVID-19, and chorioamnionitis were excluded. Genomic DNA was isolated from umbilical cord blood cells and genome-wide DNA methylation was performed using Illumina Methylation EPIC assay. A total of 155 differentially methylated loci (81 genes were hypermethylated and 74 were hypomethylated) were identified in LDA-exposed neonatal umbilical cord blood compared with the control group. Important canonical pathways identified by Ingenuity Pathway Analysis (IPA) were related to Th1 and Th2 signaling and classical (M1) macrophage activation. The genes affected by LDA exposure were associated with cardiac and renal systems. LDA exposure led to differential DNA methylation in umbilical cord blood. The differentially methylated genes were related to inflammatory pathways as well as cardiac and renal toxicity pathways. LDA exposure in utero may promote altered health programming in the neonate in areas impacting cardiovascular health. · Maternal aspirin exposure is associated with differential DNA methylation in cord blood.. · Cord blood epigenetic changes associated with maternal aspirin relate to anti-inflammatory pathways.. · Research on potential protective impact of maternal aspirin on neonatal epigenetics is warranted..

Methylation of DNA, histones, and RNA is central to the regulation of circadian rhythms, yet the biochemical origin of the methyl groups driving these modifications has received comparatively little attention in circadian biology. This review explores the bidirectional crosstalk between the methyl cycle and the mammalian circadian clock. We describe how S-adenosylmethionine-dependent epigenetic and epitranscriptomic modifications constitute essential layers of circadian gene regulation, and how the clock orchestrates the rhythmic expression of one-carbon metabolism enzymes and oscillations in S-adenosylmethionine availability. The direct interaction between the S-adenosylhomocysteine hydrolase AHCY and the core clock component BMAL1 at circadian gene promoters emerges as a molecular nexus linking methyl group supply to clock-driven transcription. We further discuss how the methyl cycle occupies a privileged position within the circadian entrainment hierarchy, acting as both a target of nutritional zeitgebers in peripheral tissues and a potential source of metabolic feedback to the central pacemaker, and how dietary perturbation of the methyl cycle disrupts circadian rhythms. Finally, we discuss how this crosstalk is implicated in metabolic liver disease, cancer, neurological disorders, and aging. Together, these findings position the circadian clock as a sensitive readout of nutritional methyl metabolic status, with broad implications for chronobiology and nutrigenomics.

Developmental-vitamin D deficiency epigenetically regulates cell cycling genes in the embryonic mesencephalon via DNA methylation.

Prenatal alcohol exposure (PAE) has a strongly documented effect on the structure and function of brain vasculature including effects on brain microvascular endothelial cell (BMVEC) behavior, impacting appropriate angiogenesis in development. We previously demonstrated that the effects of PAE on BMVEC behavior are partially mediated by the upregulation of miR-150-5p, a negative regulator of angiogenesis. Here, we characterize transcriptional mechanisms by which alcohol exposure results in upregulated miR-150-5p in BMVECs. We provide evidence for increased transcription of the miR-150 gene with alcohol exposure; specifically, we show elevated pri-miR-150 abundance, an altered miR-150 promoter methylation landscape, and overall increased miR-150 promoter activity. The alterations to the methylation landscape prompted investigation of enzymes responsible for DNA methylation dynamics, and we show altered expression of DNA methyltransferase (Dnmt) genes and Tet methylcytosine dioxygenase 1 (Tet1). We also illuminate alterations to the activation of a wide array of transcription factors throughout the nucleus as well as altered association between transcription factors and the miR-150 promoter. Overall, we uncover a novel mechanism of gene expression dysregulation by alcohol exposure in BMVECs through differential transcription factor binding as a result of altered DNA methylation mediated primarily by elevated Tet1.NEW & NOTEWORTHY Elevation of miR-150-5p in the brain vasculature during prenatal alcohol exposure occurs partially through increased transcription. This increase in transcription is mediated by the upregulation of Tet1; the elevated TET1 protein partially demethylates the miR-150 promoter into a 5hmC-rich sequence. Consequently, transcription factor binding to the promoter sequence is altered, resulting in increased miR-150 transcription.

Neonatal inflammation induces ventral hippocampal microglial priming via epigenetic regulation of BAG3 to enhance adult depression susceptibility in mice.

Hypoxia-reoxygenation alters global and gene-specific DNA methylation of GAPDH, independently of its expression and enzyme activity in the shrimp Penaeus vannamei.

DNA Methylation in Dilated Cardiomyopathy and Response to LVAD Therapy

Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental conditions characterized by deficits in social communication and the presence of restricted, repetitive behaviors. While genetic factors contribute substantially to ASD etiology, growing evidence highlights the role of environmental and epigenetic factors, with maternal stress during pregnancy emerging as a potential determinant of fetal brain development. Prenatal stress may alter the intrauterine environment through modulation of the hypothalamic-pituitary-adrenal (HPA) axis and changes in glucocorticoid signaling. These physiological responses have been associated with epigenetic modifications, such as DNA methylation, histone post-translational modifications, and alterations in non-coding RNA expression although causal pathways remain under investigation. Consequently, gene expression programs critical for neuronal proliferation, migration, synaptogenesis, and stress-response maturation are reshaped. Converging evidence from human cohorts and animal models indicates that these stress-induced epigenetic changes affect genes such as NR3C1, FKBP5, BDNF, OXTR, and SHANK3, contributing to altered stress response, impaired synaptic plasticity, and disrupted neural connectivity. Foundational studies before2020 established the basic mechanistic link between prenatal stress, glucocorticoid exposure, and epigenetic gene regulation, forming a basis for the 2020-2025 literature summarized here. This narrative review synthesizes research published between 2020 and 2025, integrating molecular, epidemiological, and neurodevelopmental perspectives to elucidate how prenatal stress induces lasting neurobiological changes, thereby advancing the conceptual framework for early detection and intervention in ASD.

Expression dynamics and promoter regulation of Caspase 6 and Caspase 7 during embryogenesis of hybrid crucian carp (Carassius auratus) × common carp (Cyprinus carpio)

Rice (Oryza sativa), a major crop, faces significant threats from various pathogens, which affect global food security. Recent research in plant biology highlights the crucial role of epigenetic mechanisms in regulating rice immunity. Epigenetics involves heritable changes in gene expression without alterations to the DNA sequence, mediated by DNA methylation, histone modifications, and non-coding RNAs. This review critically evaluates the role of epigenetics in rice immunity, focusing on key epigenetic modifications and their impact on disease resistance, including WRKY transcription factors and epigenetic regulatory factors, such as RdDM (RNA-directed DNA methylation). These epigenetic regulators enable rice plants to dynamically withstand pathogen attacks by modulating the expression of defense-related genes. This review evaluates the epigenetic responses of rice to major pathogens, including Magnaporthe oryzae (M. oryzae) and Xanthomonas oryzae (Xoo). We move beyond simple descriptions of epigenetic marks to analyze the functional integration of these pathways and their trade-offs with plant growth. Finally, we discuss the potential of "epigenetic breeding" and CRISPR-based epi-editing as a sustainable frontier for developing broad-spectrum resistance in rice. Future research should focus on identifying specific epigenetic markers associated with resistance traits and integrating epigenetic approaches with traditional breeding and biotechnological methods to achieve sustainable rice production and ensure food security in the face of evolving pathogen threats.

Crosstalk of pathogenic signaling pathways in intervertebral disc degeneration: Epigenetic regulation and therapeutic implications.

Identification and functional characterization of wheat calmodulin-like proteins reveals the role of TaCML22 and TaCML40 in defense response against Fusarium graminearum infection.

In soft tissue pathology, MUC4 is considered a sensitive and specific immunohistochemical marker for low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF), which are characterized by FUS/EWSR1 :: CREB3L2/1 fusions. Recently, MUC4-positive fibroblastoma has been proposed as a novel entity, and we herein describe 7 cases that align with this disease concept. These tumors occurred in 7 female patients aged 14 to 60 years, and they were located in the neck (2 cases), temple, arm, chest wall, pharynx, and thigh, with 5 being deep-seated. All tumors were surgically removed. No patients experienced recurrence during follow-up periods of 2 to 113 months. The well-circumscribed tumors comprised hypocellular fibrous tissue, populated by nonatypical spindle cells. Myxoid stroma was absent. Common features included thin-walled patent vessels, extremely long vessels, and mast cells. In some cases, fat entrapment/overgrowth was conspicuous. All tumors tested positive for MUC4 and nuclear β-catenin expression. The tumors were molecularly investigated with fluorescence in situ hybridization, RNA sequencing, DNA panel sequencing, DNA methylation analysis, and/or nanopore sequencing. Genetic analysis showed the absence of FUS/EWSR1 fusions in all 7 cases. All 5 tested tumors harbored APC alterations, with 3 having inactivating mutations and 2 showing copy number loss. DNA methylation profiles of 2 tumors did not match those of any references, including LGFMS or SEF, as indicated by t-SNE. Overall, our study supports the recent proposal of MUC4-positive fibroblastoma as a distinct entity and further delineates its phenotypic and molecular characteristics. These tumors should be distinguished from LGFMS, SEF, desmoid fibromatosis, and other fibrous or fibroadipose tumors.

Choline, a nexus for neurocognitive nutrients: A narrative review.