DNA Methylation Patterns Research Articles

Identification of DNA Methylation Differences in Pituitary Tissues of Sichuan White Geese Using Whole-Genome Bisulfite Sequencing (WGBS)

To explore the impact of epigenetic modifications on egg-laying traits in geese, we employed genome-wide bisulfite sequencing (WGBS) to analyze DNA methylation patterns in pituitary tissues of high-(HYP) and low-yield (LYP) Sichuan White geese. We achieved high-quality sequencing data (mean 19.09 Gb raw reads, 15.49 Gb clean reads, 79.1% unique mapping rate) with a bisulfite conversion efficiency of 99.88%. Comparative analysis revealed 2394 differentially methylated regions (DMRs) and 422 differentially methylated genes (DMGs) between HYP and LYP groups. We identified five key differentially methylated candidate genes (BMPER, INHA, NMBR, NK3R, and DSG2) linked to egg-laying traits in Sichuan White geese. Integrated GO and KEGG enrichment analysis conducted to explore the role of regulatory networks of epigenetic modification on egg-laying traits in Sichuan White geese identified multiple metabolic pathways associated with egg-laying traits (promoting egg transport, ovulation, and yolk protein synthesis and secretion), thus providing a basis for subsequent functional verification.

The Impact of Air Pollution on Sperm DNA Methylation.

A number of environmental factors have been shown to impact the sperm epigenome. Air pollution is one of the largest health and environmental hazards in the world today and has been implicated in many modern diseases. Recently, air pollution has been shown to alter methylation signatures in some body tissues, indicating that air pollution may also affect the sperm epigenome. The present experiment was conducted to analyze how seasonal air pollution in the Salt Lake Valley may impact DNA methylation patterns in sperm and to establish a relationship between air pollution and sperm epigenetic health as measured by DNA methylation. Sperm DNA methylation patterns were assessed in 74 individuals, who presented at the University of Utah Andrology Clinic for semen analysis, using the Illumina Human MethylationEPIC BeadChip array. Each semen sample collected, as per the fifth edition of WHO reference values for human semen characterization, was deemed normal. Two sample groups from the Salt Lake Valley, Urban Winter (UW, n=20), Urban Summer (US, n=21), and two sample groups east of the Wasatch mountains, Rural Winter (RW, n=19) and Rural Summer (RS, n=14), were compared to assess the effect of air pollution on sperm DNA methylation patterns. Due to seasonal inversions, urban winters are characterized by increased air pollution compared to summer months. Therefore, the UW sample group was designated as treatment and the three remaining groups (US, RW, RS) were designated as control. We conducted multiple differential methylation analyses using a sliding window approach which utilized the USeq software package. A sliding window analysis of UW versus US was conducted first, followed by a confirmatory analysis comparing UW versus RW and RS. Outputs from the USeq analysis were assessed using several tools including the Stanford GREAT analysis and an analysis of methylation instability at key promoter regions in sperm. The sliding window analysis identified six differentially methylated regions (DMRs) between the UW and US groups (Wilcoxon FDR ≥ 40, corresponding p-value of ~0.0001). Three of these six regions were confirmed with the second confirmatory analysis of UW versus RS/RW (Wilcoxon FDR ≥ 20, p-value<0.01). According to a GREAT analysis, each of the identified regions exhibited multiple gene ontology associations. Air pollution subtly alters DNA methylation in sperm, indicating that certain regions of the sperm epigenome may be susceptible to air pollution-induced modification with possible implications for reproductive and offspring health.

Integrated analysis of methylome and transcriptome responses to exercise training in children with overweight/obesity.

We examined the effects of a 20-wk exercise intervention on whole blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.39 yr, 56% girls) with OW/OB were randomized to either a 20-wk exercise intervention [exercise group (EG); n = 10; 4 boys/6 girls] or to usual lifestyle [control group (CG); n = 13; 6 boys/7 girls]. Whole blood genome-wide methylome (CpG sites) analysis using Infinium Methylation EPIC array and transcriptome analysis using RNA-seq (STRT2 protocol) were performed. Exercise-induced modifications in DNA methylation at 485 and 386 CpGs sites in boys and girls, respectively. These CpG sites are mapped to loci enriched in distinct gene pathways related to metabolic diseases, fatty acid metabolism, and immune function. In boys, changes in the DNA methylation of 87 CpG sites (18% of the 485 CpGs sites altered by exercise) were associated with changes in the gene expression levels of 51 genes also regulated by exercise. Among girls, changes in DNA methylation at 46 CpG sites (12% of the initial 386 significant CpGs) were associated with changes in the expression levels of 30 exercise-affected genes. Genes affected by exercise that were associated with DNA methylation are related to obesity, metabolic syndrome, and inflammation. Multiomics analysis of whole blood samples from children with OW/OB suggests that gene expression response to exercise may be modulated by DNA methylation and involve gene pathways related to metabolism and immune functions.NEW & NOTEWORTHY This study pioneers the exploration into the effects of exercise on whole blood genome-wide DNA methylation patterns and its association with changes in transcriptome profiles in children with overweight/obesity. Exercise potentially impacts molecular pathways involved in metabolism and immune functions in children with overweight/obesity (sex-specific responses) through the modification of epigenetic and transcriptomic profiles. Our preliminary results provide initial steps to understand better the molecular mechanisms underlying cardiometabolic benefits of exercise in children with overweight/obesity.

DNA methylation-based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity.

Sex differences in life span are widespread across animal taxa, but their causes remain unresolved. Alterations to the epigenome are hypothesized to contribute to vertebrate aging, and DNA methylation-based aging clocks allow for quantitative estimation of biological aging trajectories. Here, we investigate the influence of age, sex, and their interaction on genome-wide DNA methylation patterns in the brown anole (Anolis sagrei), a lizard with pronounced female-biased survival and longevity. We develop a series of age predictor models and find that, contrary to our predictions, rates of epigenetic aging were not slower in female lizards. However, methylation states at loci acquiring age-associated changes appear to be more "youthful" in young females, suggesting that female DNA methylomes are preemptively fortified in early life in opposition to the direction of age-related drift. Collectively, our findings provide insights into epigenetic aging in reptiles and suggest that early-life epigenetic profiles may be more informative than rates of change for predicting sex biases in longevity.

Epigenetic state and gene expression remain stable after CRISPR/Cas-mediated chromosomal inversions.

The epigenetic state of chromatin, gene activity and chromosomal positions are interrelated in plants. In Arabidopsis thaliana, chromosome arms are DNA-hypomethylated and enriched with the euchromatin-specific histone mark H3K4me3, while pericentromeric regions are DNA-hypermethylated and enriched with the heterochromatin-specific mark H3K9me2. We aimed to investigate how the chromosomal location affects epigenetic stability and gene expression by chromosome engineering. Two chromosomal inversions of different sizes were induced using CRISPR/Cas9 to move heterochromatic, pericentric sequences into euchromatic regions. The epigenetic status of these lines was investigated using whole-genome bisulfite sequencing and chromatin immunoprecipitation. Gene expression changes following the induction of the chromosomal inversions were studied via transcriptome analysis. Both inversions had a minimal impact on the global distribution of histone marks and DNA methylation patterns, although minor epigenetic changes were observed across the genome. Notably, the inverted chromosomal regions and their borders retained their original epigenetic profiles. Gene expression analysis showed that only 0.5-1% of genes were differentially expressed genome-wide following the induction of the inversions. CRISPR/Cas-induced chromosomal inversions minimally affect epigenetic landscape and gene expression, preserving their profiles in subsequent generations.

Epigenetic mechanisms underlying endometrial cancer (EC) outcomes: race-specific patterns of DNA methylation associated with molecular subtypes and survival.

Endometrial cancer [EC] is the fourth most common cancer in women in the United States. Stark racial disparities are present in EC outcomes in which Black women have significantly higher EC-related mortality than White women. The social and biologic factors that contribute to these disparities are complex, and may include racial differences in epigenetic landscapes. To investigate race-specific epigenetic differences in EC tumor characteristics and outcomes, we utilized the most recent data within the Cancer Genome Atlas (TCGA). Genome-wide CpG methylation data for more than 850 000 CpG sites were analyzed across 245 tumor samples, including 52 from Black women and 181 from White women. Race-adjusted and race-stratified associations among CpG methylation in ECs and molecular subtypes and disease-free survival (DFS) were examined. Race-specific analysis identified subtype-associated CpGs within 9572 genes in tumors from White women, and only 10 genes in tumors that were from Black women. Race-specific analyses also identified survival-associated CpGs with 1119 unique genes identified in tumors from White women, and none identified in tumors from Black women. Genes identified with differential methylation among subtypes included those involved in oxidative stress (HIF3A), and DNA repair (MLH1). Replication cohort data highlighted genes overlapping with those identified within the TCGA, such as G Protein Subunit Beta 1 (GNB1), involved in G-protein signaling, and Interleukin 37 (IL37), involved in cytokine signaling. Identification of these racial differences in EC tumor epigenetic landscapes and associated changes in gene expression may provide insight into strategies to improve outcomes and reduce disparities.

Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets

Hidradenitis suppurativa (HS) is a chronic skin condition that primarily affects areas with dense hair follicles and apocrine sweat glands, such as the underarms, groin, buttocks, and lower breasts. Intense pain and discomfort in HS have been commonly noted, primarily due to the lesions’ effects on nearby tissues. Pain is a factor that can influence DNA methylation patterns, though its exact role in HS is not fully understood. We aim to identify molecular markers of chronic pain in HS patients. We performed DNA methylome of peripheral blood DNA derived from a group of 24 patients with HS and 24 healthy controls, using Illumina methylation array chips. We identified 253 significantly differentially methylated CpG sites across 253 distinct genes regulating pain sensitization in HS, including 224 hypomethylated and 29 hypermethylated sites. Several genes with pleiotropic roles include transporters (ABCC2, SLC39A8, SLC39A9), wound healing (MIR132, FGF2, PDGFC), ion channel regulators (CACNA1C, SCN1A), oxidative stress mediators (SCN8A, DRD2, DNMT1), cytochromes (CYP19A, CYP1A2), cytokines (TGFB1, IL4), telomere regulators (CSNK1D, SMAD3, MTA1), circadian rhythm (IL1R2, ABCG1, RORA), ultradian rhythms (PHACTR1, TSC2, ULK1), hormonal regulation (PPARA, NR3C1, ESR2), and the serotonin system (HTR1D, HTR1E, HTR3C, HTR4, TPH2). They also play roles in glucose metabolism (POMC, IRS1, GNAS) and obesity (DRD2, FAAH, MMP2). Gene ontology and pathway enrichment analysis identified 43 pathways, including calcium signaling, cocaine addiction, and nicotine addiction. This study identified multiple differentially methylated genes involved in chronic pain in HS, which may serve as biomarkers and therapeutic targets. Understanding their epigenetic regulation is crucial for personalized pain management and could enhance the identification of high-risk patients, leading to better preventative therapies and improved maternal and neonatal outcomes.

Intraspecific epigenomics divergence in brown bears (Ursus arctos): insights from genome-wide DNA methylation patterns

Epigenetic mechanisms such as methylation can influence gene expression and play a crucial role in the adaptation to local environmental conditions, thereby introducing non-genetic variability within species. Here, using a Reduced Representation Bisulfite Sequencing approach (RRBS), we compared the methylation patterns in blood and muscle across three European brown bear populations. Our results clearly demonstrated that, beyond tissue-driven divergences, the methylation patterns of the three populations are significantly distinct. Differentially methylated sites, possibly associated with genomic features involved in development and anatomical differentiation, are widespread across the bear genome. This finding supports previous studies suggesting a role for the alteration of developmental pathways in shaping phenotypic novelties with potential adaptative significance. Our results underscore the importance and the effectiveness of including epigenetic approaches in studying wild non-model organisms. Investigating the epigenome can be especially relevant for endangered populations that have experienced a significant erosion of genomic diversity.

Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: potential use as sepsis biomarkers

IntroductionSepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.MethodsA prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.ResultsSignificant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).DiscussionOur results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.

MethylGrapher: genome-graph-based processing of DNA methylation data from whole genome bisulfite sequencing.

Genome graphs, including the recently released draft human pangenome graph, can represent the breadth of genetic diversity and thus transcend the limits of traditional linear reference genomes. However, there are no genome-graph-compatible tools for analyzing whole genome bisulfite sequencing (WGBS) data. To close this gap, we introduce methylGrapher, a tool tailored for accurate DNA methylation analysis by mapping WGBS data to a genome graph. Notably, methylGrapher can reconstruct methylation patterns along haplotype paths precisely and efficiently. To demonstrate the utility of methylGrapher, we analyzed the WGBS data derived from five individuals whose genomes were included in the first Human Pangenome draft as well as WGBS data from ENCODE (EN-TEx). Along with standard performance benchmarking, we show that methylGrapher fully recapitulates DNA methylation patterns defined by classic linear genome analysis approaches. Importantly, methylGrapher captures a substantial number of CpG sites that are missed by linear methods, and improves overall genome coverage while reducing alignment reference bias. Thus, methylGrapher is a first step toward unlocking the full potential of Human Pangenome graphs in genomic DNA methylation analysis.

DOP039 Dietary methyl group donor intake alleviates the susceptibility to inflammatory bowel disease influenced by environmental pollution in a prospective cohort study

Abstract Background Both genetic and environmental factors play crucial roles in individual susceptibility to inflammatory bowel disease (IBD) [1], though its exact etiology remains unclear. Multiple studies have identified environmental pollutants, such as cigarette smoke and fine particulate matter, as significant risk factors for IBD [2, 3]. Chronic exposure to air pollution alters DNA methylation patterns, with a typically long-term hypomethylated status. Our previous study also found that smoking can lead to susceptibility to IBD by affecting the methylation levels of key genes [2]. Moreover, DNA methylation, as an epigenetic mechanism, has been implicated in the pathogenesis of IBD. The intake and quality of dietary methyl group donors (MGDs) directly affects the methylation process in vivo, potentially modulating the risk of developing IBD. Therefore, the present study explored the effect of dietary MGDs on the development of IBD and whether dietary MGDs intake is beneficial in modulating the susceptibility to IBD influenced by environmental pollution. Methods We included 186,195 IBD-free participants at baseline with available dietary information from UK Biobank. Dietary MGDs intake was aggerated by the z-score of methionine, folate, choline, betaine intake by 24h dietary recalls. Smoking behavior and intensity were ascertained via self-report questionnaires. Susceptibility to air pollution was estimated by summing up the exposure to four air pollutant (PM2.5, PM10, NOx, NO2) weighted by effect size on liability to IBD [3, 4]. Diagnosis of IBD were determined by at least two health-related records in national registries. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 10.8 years, we identified 139 and 285 incident cases of CD and UC. We found that individuals with the highest quintiles of dietary MGDs have a significant reduction in risk of CD (HR 0.50, 95% CI 0.28-0.90, P=0.021; P-trend=0.018) and UC (HR 0.62, 95% CI 0.40-0.96, P=0.034; P-trend=0.022) compared to those in the lowest quintile (Figure 1). The associations between dietary MGD and CD were more pronounced in individuals with smoking history (HR 0.66, 95% CI 0.51-0.86), who smoke more than 20 pack-years (HR 0.63, 95% CI 0.45-0.86), who were exposed to high air pollution (HR 0.58, 95% CI 0.37-0.91) than individuals without smoking history, who smoke less than 20 pack-years, who exposed to lower air pollution (all P-interaction&amp;lt;0.05, Figure 4). Conclusion This study demonstrates the potential of dietary methyl donors for the prevention of IBD and provides more precise nutritional intervention strategies for populations affected by smoking and air pollution problems.

MethylBERT enables read-level DNA methylation pattern identification and tumour deconvolution using a Transformer-based model

DNA methylation (DNAm) is a key epigenetic mark that shows profound alterations in cancer. Read-level methylomes enable more in-depth analyses, due to their broad genomic coverage and preservation of rare cell-type signals, compared to summarized data such as 450K/EPIC microarrays. Here, we propose MethylBERT, a Transformer-based model for read-level methylation pattern classification. MethylBERT identifies tumour-derived sequence reads based on their methylation patterns and local genomic sequence, and estimates tumour cell fractions within bulk samples. In our evaluation, MethylBERT outperforms existing deconvolution methods and demonstrates high accuracy regardless of methylation pattern complexity, read length and read coverage. Moreover, we show its applicability to cell-type deconvolution as well as non-invasive early cancer diagnostics using liquid biopsy samples. MethylBERT represents a significant advancement in read-level methylome analysis and enables accurate tumour purity estimation. The broad applicability of MethylBERT will enhance studies on both tumour and non-cancerous bulk methylomes.

Transcriptome and DNA methylation analysis of the goat pineal gland during puberty

Previous studies have confirmed that methylation regulates gene transcription in the hypothalamus-pituitary-gonadal axis during puberty initiation, but little is known about the regulation of DNA methylation on gene expression in the pineal gland. To screen pineal gland candidate genes related to the onset of goat puberty and regulated by genome methylation, we collected pineal glands from prepubertal and pubertal female goats, then, determined the DNA methylation profile by whole genome bisulfite sequencing and the transcriptome by RNA sequencing on Illumina HiSeqTM2500. We analyzed differentially expressed genes between the Pre group and Pub group using the DESeq2 software (version 1.20.0), and applied the Benjamini and Hochberg method for adjusting P-values. Genes with a P-value less than 0.05 and an absolute log2 fold change greater than 0 were considered differentially expressed genes. Results showed that there was no significant difference in the whole-genome methylation level of the pineal gland between prepubertal and pubertal goats, but the methylation pattern changed significantly, indicating that genomic DNA methylation of the pineal gland might play a role in regulating the initiation of goat puberty. Changes in DNA methylation patterns affected some pineal gland transcriptomes, while the transcriptional level of most genes remained unaffected by DNA methylation differences. Genes regulated by DNA methylation regulates genes primarily involved in metabolic processes, oxidative phosphorylation, and signaling pathways related to thermogenesis. Methylation significantly regulated the expression of genes such as ATP5F1D, CACNB2, and PTEN, while genes like LIN28B, GIP, OPN1SW, and DCC showed the most notable fold changes, which may indicate their involvement in the onset of puberty.

Harnessing Nanomaterials for Next-Generation DNA Methylation Biosensors.

DNA methylation is an epigenetic mechanism that regulates gene expression and is implicated in diseases such as cancer and atherosclerosis. However, traditional clinical methods for detecting DNA methylation often lack sensitivity and specificity, making early diagnosis challenging. Nanomaterials offer a solution with their unique properties, enabling highly sensitive photochemical and electrochemical detection techniques. These advanced methods enhance the accuracy and efficiency of identifying DNA methylation patterns, providing a powerful tool for early diagnosis and treatment of methylation-related diseases. This review summarizes nanomaterial-based techniques, categorized into electrochemical and photochemical methods for developing next-generation biosensors for DNA methylation. Electrochemical approaches based on nanostructured or nanomaterial-modified electrodes can detect methylation through electrical signals and can directly identify methylation sites via ionic current changes based on nanopore sequencing. Photochemical methods based on nanoparticles allow for optical detection through colorimetry, fluorescence, surface plasmon resonance, and Raman spectroscopy. Nanotechnology-implemented methodologies enable ultrasensitive and selective biosensors as point-of-care platforms for DNA methylation analysis, thereby advancing epigenetic research and clinical diagnostics.

DNA methylation patterns are influenced by Pax3::Foxo1 expression and developmental lineage in rhabdomyosarcoma tumours forming in genetically engineered mouse models.

Rhabdomyosarcoma (RMS) is a family of phenotypically myogenic paediatric cancers consisting of two major subtypes: fusion-positive (FP) RMS, most commonly involving the PAX3::FOXO1 fusion gene, formed by the fusion of paired box 3 (PAX3) and forkhead box O1 (FOXO1) genes, and fusion-negative (FN) RMS, lacking these gene fusions. In humans, DNA methylation patterns distinguish these two subtypes as well as mutation-associated subsets within these subtypes. To investigate the biological factors responsible for these methylation differences, we profiled DNA methylation in RMS tumours derived from genetically engineered mouse models (GEMMs) in which various driver mutations were introduced into different myogenic lineages. Our unsupervised analyses of DNA methylation patterns in these GEMM tumours yielded two major clusters, corresponding to high and no/low expression of Pax3::Foxo1, which mirrored the results for human FP and FN RMS tumours. Two distinct methylation-defined subsets were found for GEMM RMS tumours with no/low Pax3::Foxo1 expression: one subset enriched in Pax7 lineage tumours and a second subset enriched in myogenic factor 5 (Myf5) lineage tumours. Integrative analysis of DNA methylation and transcriptomic data in mouse and human RMS revealed a common group of differentially methylated and differentially expressed genes, highlighting a conserved set of genes functioning in both human RMS models and GEMMs of RMS. In conclusion, these studies provide insight into the roles of oncogenic fusion proteins and developmental lineages in establishing DNA methylation patterns in FP and FN RMS respectively. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Epigenetic Mechanisms in Neurodegenerative Diseases: Advances in Molecular Research

Recent advances in molecular biology have revolutionized our understanding of neurodegenerative disorders, revealing the intricate interplay between epigenetic mechanisms and disease progression. This review synthesizes emerging evidence on how epigenetic modifications, including DNA methylation patterns, histone alterations, and non-coding RNA (ncRNA) dynamics, orchestrate neural degeneration and potential therapeutic interventions. We critically examine how aberrant epigenetic signatures in genes such as APP and SNCA drive pathological cascades in conditions like Alzheimer's disease (AD) and Parkinson's disease (PD). Through systematic analysis of recent literature, we evaluate the diagnostic potential of epigenetic biomarkers and explore promising therapeutic strategies targeting these modifications. This comprehensive review provides a framework for understanding epigenetic mechanisms in neurodegeneration while highlighting innovative approaches for clinical intervention.

DNA Methylation of Somatic Tissues in Oysters is Influenced by Sex and Heredity.

The influence of sex and heredity on DNA methylation in the somatic tissues of mice has been well-documented, with similar hereditary effects reported in honeybees. However, the extent to which these factors affect DNA methylation in molluscan somatic tissues remains poorly understood. In this study, we investigated genomic DNA methylation patterns in the adductor muscle of two genetically distinct oyster strains using whole-genome bisulfite sequencing (WGBS). Our analysis identified significant differences in DNA methylation between sexes, with females exhibiting a global reduction compared to males. Furthermore, approximately half of the differentially methylated sites between the two parental strains were conserved in their offspring. Regions with differential methylation in parents typically exhibited intermediate methylation levels in the F1 progeny, whereas consistently methylated regions in parents maintained similar methylation levels in their progeny. These findings suggest that offspring DNA methylation is strongly influenced by parental methylation profiles, highlighting its potential role in sexual determination in oysters.

Longitudinal DNA methylation profiles in saliva of offspring from mothers with gestational diabetes: associations with early childhood growth patterns

BackgroundThe prevalence of obesity and type 2 diabetes mellitus (T2DM) is rising globally, particularly among children exposed to adverse intrauterine environments, such as those associated with gestational diabetes mellitus (GDM). Epigenetic modifications, specifically DNA methylation, have emerged as mechanisms by which early environmental exposures can predispose offspring to metabolic diseases. This study aimed to investigate DNA methylation differences in children born to mothers with GDM compared to non-GDM mothers, using saliva samples, and to assess the association of these epigenetic patterns with early growth measurements.MethodsThis study analyzed saliva DNA methylation patterns in 30 children (15 born to GDM mothers and 15 to non-GDM mothers) from the EPIDG cohort. Samples were collected at two time points: 8–10 weeks postpartum and at one year of age. Epigenome-wide analysis of over 850,000 CpG sites was conducted using the Illumina Methylation EPIC Bead Chip. Differential methylation positions (DMPs) were identified with the limma package, using a significance threshold of p < 0.01 and delta β ≥ 5%. Correlation analysis examined associations between methylation and growth variables (weight, height, BMI and annual growth) using Spearman tests.ResultsWe identified 6,968 DMPs at the postpartum stage and 5,132 after one year, with 50 sites remaining differentially methylated over time, 16 of which maintained consistent methylation directionality. Functional analysis linked several of these DMPs to genes involved in inflammation and metabolic processes, including CYTH3 and FARP2, both implicated in growth and metabolic pathways. Significant correlations were found between specific CpG sites and growth-related variables such as weight, head circumference, height, and BMI.ConclusionsThis study’s longitudinal design reveals stable DNA methylation patterns in saliva samples that differentiate GDM-exposed children from controls across the first year of life, highlighting the feasibility of saliva as a minimally invasive biomarker source. The persistence of these epigenetic signatures underscores their potential as early indicators of metabolic risk, offering valuable insights into the long-term impact of maternal GDM on child health. Although the use of saliva offers a practical and non-invasive tool for pediatric epigenetic research, further studies are necessary to validate these findings in larger populations.

Site-specific DNA demethylation during spermatogenesis presets the sites of nucleosome retention in mouse sperm.

DNA methylation patterns are inherited from the parental germline to the embryo. In mature sperm, the sites of unmethylated DNA are tightly coupled to sites of histone retention at gene regulatory elements that are implicated in paternal epigenetic inheritance. The timing and mechanism of site-specific DNA demethylation in the male germline currently remains unknown. Here, we perform genome-wide profiling of DNA methylation during spermatogenesis by capturing methylated DNA through interaction with a methyl-DNA binding protein domain (MBD). Our data demonstrate that there is a site-specific change in DNA methylation during the mitosis-to-meiosis transition. Importantly, the genomic sites that are demethylated during this transition predetermine nucleosome retention sites in spermatozoa. These results suggest that site-specific DNA demethylation during the mitosis-to-meiosis transition of spermatogenesis prepares embryonic gene expression after fertilization. We therefore propose DNA demethylation during spermatogenesis as a novel phase of epigenetic reprogramming that contributes to embryonic gene regulation.

Comprehensive analysis of DNA methylation and gene expression to identify tumor suppressor genes reactivated by MLN4924 in acute myeloid leukemia.

This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profiles of Kasumi-1 and KU812 acute myeloid leukemia cell lines before and after MLN4924 treatment were generated using the 850K Methylation BeadChip. RNA sequencing was used to obtain transcriptomic profiles of Kasumi-1 cells. Target genes were identified through a combined analysis of methylation and transcriptome data. Methylation-specific PCR and quantitative PCR validated the changes in methylation and expression. Prognostic analysis of target genes was performed using databases, and Pearson correlation was used to examine the relationship between methylation and expression levels. In Kasumi-1 and KU812 cells, 301 and 469 differentially methylated sites, respectively, were identified. A total of 4310 differential expression genes were detected in Kasumi-1. Combined analysis revealed that TRIM58 exhibited significant demethylation and upregulation after MLN4924 treatment, as confirmed by quantitative and methylation-specific PCR. Furthermore, database analysis revealed that both down-expression and promoter hypermethylation of TRIM58 were correlated with poor prognosis in acute myeloid leukemia. A negative correlation was observed between TRIM58 methylation and expression levels. This study suggests that MLN4924 alters DNA methylation patterns in acute myeloid leukemia and reactivates TRIM58, a potential tumor suppressor gene, through demethylation.