Epigenomics最新文献

Aims: Epidemiological studies of DNA methylation often use buccal swabs, which contain mixtures of cell types, but no low-cost methods exist for statistical correction in candidate gene studies using targeted bisulfite sequencing. This study aims to address this gap by estimating the proportion of buccal epithelial cells in swab and mouthwash samples.

Materials & methods: We applied a recently described and smoothly to implement method for estimating the proportion of buccal epithelial cells in buccal swab and mouthwash samples using targeted bisulfite sequencing. Additionally, we investigated the methylation of actinin alpha 3 (ACTN3), a marker for cell type-specific methylation, following psychosocial and physical stress.

Results: The proposed estimation method showed strong correlation with the EpiDISH algorithm and effectively controlled for cellular heterogeneity. Over 90% of the variance in ACTN3 methylation was explained by including the epithelial cell proportion in the model.

Conclusion: Our findings provide a solution for controlling cellular heterogeneity in buccal swab and mouthwash DNA methylation studies. This method is particularly relevant for candidate gene studies in clinical settings, but future work should refine it for more detailed analyses of cell type proportions to improve precision.

Aims: This research aims to establish a chromatin regulator (CR) signature to provide new epigenetic insights into the pathogenesis of primary open-angle glaucoma (POAG).

Materials & methods: The expression profile of CRs in trabecular meshwork (TM) tissues was analyzed by bioinformatics analysis; The selected hub CRs were further verified by cell experiments.

Results: We found the immune microenvironment of the TMwas changed in POAG patients and identified 3 differentially expressed CRs that were relevant to immunity. Then, we successfully constructed and proved a predicted signature based on these 3 CRs, which could effectively predict the risk of POAG. The genes co-expressed with these 3 CRs and miRNAs with are gulatory relationship were identified, and a miRNA-hub CR network was successfully constructed. The results of the Gene Set Enrichment analysis indicated that these 3 hub CRs were all associated with neurodegenerative diseases. Moreover, the human trabecular meshwork cell (HTMC) oxidative stress model was constructed, and KDM5B was significantly down-regulated in this cell model. Finally, we found 10 agents that might be helpful for patients with POAG.

Conclusions: Dysregulation of CR expression in TM tissues may be involved in the occurrence and progression of POAG through multiple mechanisms.

Gastrointestinal (GI) cancers impose a significant disease burden, underscoring the critical importance of accurate prognosis prediction and treatment response evaluation. DNA methylation, one of the most extensively studied epigenetic modifications, has gained prominence due to its reliable measurement across various sample types. Numerous studies have reported that DNA methylation was linked to the diagnosis, prognosis and treatment response in malignancies, including GI cancers. While its diagnostic role in GI cancers has been comprehensively reviewed. Recent research has increasingly highlighted its potential in prognosis prediction and treatment response evaluation. However, no existing reviews have exclusively focused on these two aspects. In this review, we retrieved relevant studies and included 230 of them in our discussion, thereby providing an overview of the clinical applicability of aberrant DNA methylation in these two fields among patients with esophageal, gastric, colorectal, pancreatic cancers, and hepatocellular carcinomas. Additionally, we discuss the limitations of the current literature and propose directions for future research. Specifically, we emphasize the need for standardized DNA methylation methodologies and advocate for the integration of gene panels, rather than single genes, to address tumor heterogeneity more effectively.

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.