Epigenomics最新文献

Aim: People living with HIV (PLWH) have an increased risk for lifetime trauma and mental health difficulties. However, no studies have evaluated stress-related genes in relation to early-life adversity, lifetime trauma, or post-traumatic stress disorder (PTSD) in PLWH.

Methods: Using bisulfite pyrosequencing, we evaluated DNA methylation (DNAm) in intron 7 of FKBP5, a glucocorticoid feedback regulator, and in the promoter of SLC6A4, the serotonin transporter gene, in whole blood of a random sample of 70 PLWH recruited from an HIV program, and 51 individuals 2 years later (n = 48 at both time points). Exploratory regression analyses were conducted with DNAm in relation to trauma exposure, mental health symptoms, and coping strategies.

Results: Higher DNAm at one site of SLC6A4 was associated with lower levels of anxiety (B = -0.62 (SE = 0.23), p = 0.0109), depression (B = -0.06 (SE = 0.03), p = 0.0435), and PTSD symptoms at baseline (B = -0.03 (SE = 0.01), p = 0.0374). DNAm at FKBP5 was negatively associated with measures of anxiety (B = -0.30 (SE = 0.07), p = 0.0001) and depression symptoms (B = -0.2 (SE = 0.10), p = 0.0103). Various coping strategies were also associated with sites in both genes across time points, e.g. self-blame and substance use.

Conclusion: Our findings generate intriguing hypotheses linking mental health symptoms and DNA methylation, to be replicated with larger samples.

Background: Immigrant status and citizenship influence health and well-being, yet their associations with DNA methylation (DNAm)-based biomarkers of aging - key predictors of healthspan and lifespan, also known as epigenetic aging - remain underexplored.

Methods: Using a representative sample of 2,336 United States (U.S.) adults from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition Examination Survey (NHANES), we analyzed cross-sectional associations of immigrant status and U.S. citizenship with seven epigenetic aging biomarkers: HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge2, DNAm Telomere Length, and DunedinPoAm.

Results: After adjusting for demographic factors, immigrants had 2.53-year lower GrimAge2 measures (95%CI: -3.44, -1.63, p < 0.001) compared to non-immigrants. U.S. citizens had 1.98-year higher GrimAge2 measures (95%CI: 0.66, 3.30, p = 0.005) compared to non-citizens. The GrimAge2 associations with immigrant status (β = -1.04-years, 95%CI: -1.87, -0.21, p = 0.02) and citizenship (β = 1.35-years, 95%CI: 0.38, 2.32, p = 0.02) were attenuated after adjusting for other lifestyle/health variables. Immigrant status and citizenship were associated with estimated levels of several GrimAge2 DNAm component proteins, including adrenomedullin and C-reactive protein.

Conclusion: Our results support the paradigm of the immigrant mortality advantage and highlight the potential value of epigenetic age measures in studying socioeconomic and broader factors influencing citizen and immigrant health.

Solid tumors are significant causes of global mortality and morbidity. Recent research has primarily concentrated on finding pathology-specific molecules that can be acquired non-invasively and that can change as the disease progresses or in response to treatment. The focus of research has moved to RNA molecules that are either freely circulating in body fluids or bundled in microvesicles and exosomes because of their great stability in challenging environments, ease of accessibility, and changes in level in response to therapy. In this context, there are many non-coding RNAs that can be used for this purpose in liquid biopsies. Out of these, microRNAs have been extensively studied. However, there has been an increase of interest in studying long non-coding RNAs, piwi interacting RNAs, circular RNAs, and other small non-coding RNAs. In this article, an overview of the most researched circulating non-coding RNAs in solid tumors will be reviewed, along with a discussion of the significance of these molecules for early diagnosis, prognosis, and therapeutic targets. The publications analyzed were extracted from the PubMed database between 2008 and June 2024.

N4-acetylcytidine (ac4C) is a post-transcriptional RNA modification that plays a crucial role in the epitranscriptome, influencing gene expression and cellular function. This modification occurs at the cytosine base, where an acetyl group is installed to the nitrogen at the 4th position (N4). This co-transcription modification affects RNA stability, RNA structure, and translation efficiency. Recent studies have uncovered a potential link between RNA modifications and DNA repair mechanisms, suggesting that ac4C-modified or methylated RNAs may interact with factors involved in DNA repair pathways; thus, influencing the cellular response to DNA damage. Dysregulation of modified RNAs, including ac4C RNA, has been implicated in cancer development, where aberrant levels of these RNAs may contribute to oncogenic transformation by altering genome stability and the expression of key genes regulating cell proliferation, cell cycle progression, and apoptosis. Understanding the dynamics of modified RNAs offers promising insights into the role of epitranscriptome in DNA repair processes and cancer treatment.

Aberrant expression of imprinted genes results in imprinting disorders (IDs). Differentially methylated regions (DMRs) reveal parental-origin-specific DNA methylation on CpGs and regulate the expression of the imprinted genes. One etiology of IDs is epimutation (epi-IDs) induced by some error in the establishment or maintenance of methylation imprint during the processes of gametogenesis, fertilization, or early embryonic development. Therefore, it has been a concern that assisted reproductive technologies (ART) increase the risk for the development of IDs, particularly epi-IDs. We review the effects of ART on DNA methylation of the genome, including DMRs in gametes, embryos, and offspring, and the risk of advanced parental age (a confounding factor of ART) and infertility itself for the development of IDs, particularly epi-IDs.

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.