Epigenomics最新文献

Dietary modification is a cornerstone and a primary goal for weight loss, whose effects may be related to epigenetic phenomena. In this literature review, a comprehensive search without time restriction was performed in PubMed/Medline, Cochrane, SciELO, and Scopus databases to identify epigenetic signatures related to obesity outcomes upon dietary advice. In this context, experimental studies and clinical trials have identified certain DNA methylation marks, miRNA expression profiles and histone modifications putatively associated with adiposity outcomes after different nutritional interventions. These include traditional dietary patterns, diets with different macronutrient compositions, and supplementation with fatty acids, amino acids and derivatives, methyl donors, vitamins and minerals, probiotics and prebiotics, and bioactive food compounds. Some of these epigenetic signatures have been mapped to genes involved in food intake control, adipogenesis, lipolysis, fatty acid oxidation, body fat deposition, and gut microbiota modulation. However, additional studies are still required to address dosage and follow-up variability, validation of epigenetic marks, genome-wide approaches, and appropriate statistical settings. Although more investigation is required, these insights may contribute to the characterization of epigenetic biomarkers of body weight regulation toward the prescription of tailored dietary strategies targeting the epigenome for a more precise obesity management and control.

Aim: We aim to assess association of DNA methylation (DNAm) at birth with total immunoglobulin E (IgE) trajectories from birth to late adolescence and whether such association is ethnicity-specific.

Methods: We examined the association of total IgE trajectories from birth to late adolescence with DNAm at birth in two independent birth cohorts, the Isle of wight birth cohort (IOWBC) in UK (n = 796; White) and the maternal and infant cohort study (MICS) in Taiwan (n = 60; Asian). Biological pathways and methylation quantitative trait loci (methQTL) for associated Cytosine-phosphate-Guanine sites were studied.

Results: Two total IgE trajectories, high vs. low, were inferred from each of the two cohorts. Associations of DNAm at 103 CpGs with IgE trajectories in IOWBC and at 476 CpGs in MICS were identified. Between the two cohorts, of the identified CpGs, one was in common, methQTL site cg16711274 (mapped to gene MINAR1), and 17 pathways were common with at least four linked to airway diseases.

Conclusion: The findings suggest at-birth epigenetics may explain ethnicity differences in total IgE trajectories later in life.

Background: Necrotizing enterocolitis (NEC) is an often fatal intestinal injury that primarily affects preterm infants for which screening tools are lacking. We performed a pilot analysis of DNA methylation in peripheral blood samples from preterm infants with and without NEC to identify potential NEC biomarkers.

Methods: Peripheral blood samples were collected from infants at NEC diagnosis (n = 15) or from preterm controls (n = 13). Targeted genome-wide analysis was performed to identify DNA methylation differences between cases and controls.

Results: Broad differences between NEC cases and controls were identified in distinct genomic elements. Differences between surgical NEC cases and controls were frequently associated with inflammation. Deconvolution analysis to identify cell type-specific DNA signatures revealed increases in ileal, vascular endothelial, and cardiomyocyte cell type proportions and decreases in colonic and neuronal cell type proportions in blood from NEC cases relative to controls.

Conclusions: We identified marked differences in DNA methylation of peripheral blood samples from preterm infants with and without NEC. Increased ileal cell-specific methylation signatures in the blood of infants with NEC relative to controls, with a marked increase seen in surgical cases, provides rationale for further analysis of intestinal DNA methylation signatures as biomarkers of NEC.

Histone acetylation, particularly H3 K27 acetylation (H3K27ac), is a critical post-translational modification that regulates chromatin structure and gene expression, which plays a significant role in various cancers, including breast, colon, lung, hepatocellular, and prostate cancer. However, the mechanisms of H3K27ac in tumorigenesis are not yet comprehensive, especially its epigenetic mechanisms. This review endeavors to discuss findings on the involvement of H3K27ac in carcinogenesis within the past 5 years through a literature search using academic databases such as Web of Science. Firstly, we provide an overview of the diverse landscape of histone modifications, emphasizing the distinctive characteristics and critical significance of H3K27ac. Secondly, we summarize and compare advanced high-throughput sequencing technologies that have been utilized in the construction of the H3K27ac epigenetic map. Thirdly, we elucidate the role of H3K27ac in mediating gene transcription. Fourthly, we venture into the potential molecular mechanism of H3K27ac in cancer development. Finally, we engage in discussing future therapeutic approaches in oncology, with a spotlight on strategies that harness the potential of H3K27 modifications. In conclusion, this review comprehensively summarizes the characteristics of H3K27ac and underscores its pivotal role in cancer, providing valuable insights into its potential as a therapeutic target for cancer intervention.

The U.S. Developmental Origins of Health and Disease (DOHaD) meeting is an annual conference of primarily U.S. scientists who study early life programming of health and disease. The eighth annual symposium, entitled "Exploring Translational DOHaD Science: From Cells to Communities" was held at the Rizzo Conference Center in Chapel Hill, North Carolina, from October 14 to 16, 2024. The meeting was organized by US-DOHaD President Danielle Christifano and Vice President Kaela Varberg, and other Society Council Members. This year's meeting had record attendance, with 158 attendees from diverse disciplines, and featured 10 keynote speakers, 11 platform talks, and 84 poster presentations. Four major topics were covered: 1) Early nutrition and developmental outcomes, 2) Prenatal origins of child health, 3) Developmental impacts of toxicant exposures, and 4) Metabolic origins of health. Overall, the presented research highlighted the value of studying epigenetic effects of dietary and toxic exposures early in life. Various strategies emerged to address challenges facing the field, such as harnessing the power of nationwide longitudinal birth cohorts, new methods to integrate epigenetic and environmental data across various levels, and the emerging potential of organoids to identify the causal impact of early life exposures.

Suicide continues to be a significant public health issue globally, claiming over 700,000 lives annually. It is, therefore, important to assess the suicide risk properly and provide intervention in a timely fashion. While the heritability of suicidal behavior is around 50%, it does not explain the factors involved in causality. Recent evidence suggests that gene x environment interaction plays a vital role in suicidal behavior. In this paper, we critically evaluate the association between adolescent suicidal behavior and epigenetic modifications, including DNA methylation, histone modification, and non-coding RNAs, as well as epigenetic-based treatment options. It was noted that the prevalence of suicidal behavior in adolescents varied by age and sex and the presence of psychiatric disorders. Childhood adversity was closely associated with suicidal behavior. Studies show that alterations in epigenetic modifications may increase the risk of suicidal behavior independent of mental illnesses. Because epigenetic factors are reversible, environmental enrichment or the use of pharmacological agents that can target specific epigenetic modulation may be able to reduce suicidal behavior in this population.

Aims: Atrioventricular block (AVB) is a prevalent bradyarrhythmia. This study aims to investigate the causal effects of epigenetic aging, as inferred from DNA methylation profiles on the prevalence of AVB by Mendelian randomization (MR) analysis.

Methods: Genetic instruments for epigenetic aging and AVB were obtained from genome-wide association study data in the Edinburgh DataShare and FinnGen biobanks. Univariable and multivariable MR analyses were conducted to evaluate causal associations. Additionally, we employed sensitivity tests to assess the robustness of the MR findings.

Results: MR analysis showed that genetically predicted GrimAge acceleration was significantly associated with a higher risk of AVB (inverse variance-weighted: p = 0.010, 95% confidence interval (CI) = 1.024-1.196; weighted median: p = 0.031, 95% CI = 1.009-1.215). However, no evidence supported a causal relationship between AVB and epigenetic aging. The association between epigenetic aging and AVB was established using multivariate MR analysis after adjusting for various risk factors. Sensitivity analyses confirmed the reliability and robustness of the results.

Conclusion: Our findings suggest that epigenetic aging in GrimAge may increase the risk of AVB, emphasizing the importance of addressing epigenetic aging in strategies for AVB prevention.

Cardiac development is a precisely regulated process governed by both genetic and epigenetic mechanisms. Among these, DNA methylation is one mode of epigenetic regulation that plays a crucial role in controlling gene expression at various stages of heart development and maturation. Understanding stage-specific DNA methylation dynamics is critical for unraveling the molecular processes underlying heart development from specification of early progenitors, formation of a primitive and growing heart tube from heart fields, heart morphogenesis, organ function, and response to developmental and physiological signals. This review highlights research that has explored profiles of DNA methylation that are highly dynamic during cardiac development and maturation, exploring stage-specific roles and the key molecular players involved. By exploring recent insights into the changing methylation landscape, we aim to highlight the complex interplay between DNA methylation and stage-specific cardiac gene expression, differentiation, and maturation.

Objective: Epigenetic alterations are critical regulators in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, the dynamic epigenomic landscapes are not well defined. Our previous study found that H3K27ac and H3K9me3 play important roles in regulating lipid metabolic pathways in the early stages of MASLD. However, the epigenomic status in the inflammation stages still needs to be determined.

Method: C57BL/6 male mice were fed with the methionine- and choline-deficient (MCD) or normal diet, and their serum and liver samples were collected after 6 weeks. Serum alanine aminotransferase (ALT), aspartate amino transferase (AST), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Chromatin immunoprecipitation sequencing (ChIP-Seq) for H3K27ac and H3K9me3 was performed together with RNA sequencing (RNA-seq) and key regulators were analyzed.

Results: The target genes of enhancers with increased H3K27ac and decreased H3K9me3 signals are enriched in lipid metabolism and immuno-inflammatory pathways. Il-34 and Slc7al are identified as potential regulators in MASLD.

Conclusion: Our study reveals that active enhancers and heterochromatin associated with metabolic and inflammatory genes are extensively reprogrammed in MCD-diet mice, and Il-34 and Slc7al are potentially key genes regulating the progression of MASLD.

Adaptation to challenging environmental conditions is crucial for the survival/fitness of all organisms. Alongside genetic mutations that provide adaptive potential during environmental challenges, epigenetic modifications offer dynamic, reversible, and rapid mechanisms for regulating gene expression in response to environmental changes in both evolution and daily life, without altering DNA sequences or relying on accidental favorable mutations. The widespread conservation of diverse epigenetic mechanisms - like DNA methylation, histone modifications, and RNA interference across diverse species, including plants - underscores their significance in evolutionary biology. Remarkably, environmentally induced epigenetic alterations are passed to daughter cells and inherited transgenerationally through germline cells, shaping offspring phenotypes while preserving adaptive epigenetic memory. Throughout anthropoid evolution, epigenetic modifications have played crucial roles in: i) suppressing transposable elements and viral genomes intruding into the host genome; ii) inactivating one of the X chromosomes in female cells to balance gene dosage; iii) genetic imprinting to ensure expression from one parental allele; iv) regulating functional alleles to compensate for dysfunctional ones; and v) modulating the epigenome and transcriptome in response to influence from the gut microbiome among other functions. Understanding the interplay between environmental factors and epigenetic processes may provide valuable insights into developmental plasticity, evolutionary dynamics, and disease susceptibility.