Epigenomics最新文献

Aims: To describe tDRs in human milk EVs and their associations with maternal body mass index, age, dietary indices, breastfeeding frequency, season and time of milk collection in a Latina population.

Materials & methods: We sequenced small RNAs from EVs from 109 mature human milk samples collected at 1 month after delivery in the Southern California Mother's Milk Study. We grouped tDRs using hierarchical clustering and clusters were compared across tDR characteristics. We analyzed associations of tDRs with intrinsic maternal variables (body mass index, age), maternal nutrition (caloric intake, Healthy Eating Index, Dietary Inflammatory Index), and variables related to feeding and milk collection (breastfeeding frequency, season and time of milk collection) using negative binomial models.

Results: We identified 338 tDRs expressed in 90% or more of milk EV samples, of which 113 were identified in all samples. tDR-1:26-Gly-CCC-1-M4 accounted for most reads (79%). Pathway analysis revealed a wide array of biological processes and disease mechanisms across the four tDR clusters. tDRs were associated with season of collection, time of collection, breastfeeding frequency, and the dietary inflammatory index.

Conclusions: tDRs are abundant in milk EVs and may be sensitive to maternal diet, seasonality, time of day, and breastfeeding frequency.

Aims: Mammalian genomes encode 12 proteins that contain a CXXC zinc finger domain. Most members of this family are large multi-domain proteins that function in the control of DNA methylation and histone methylation patterns. CXXC5 is a smaller member of the family, along with its closest homologue CXXC4. These two proteins lack known catalytic domains. Here, we have characterized CXXC5 in mouse embryonic stem (ES) cells.

Materials & methods: We used gene knockouts, RNA sequencing, and DNA methylation analysis by whole-genome bisulfite sequencing.

Results & conclusions: We show that CXXC5 is a nuclear protein that interacts with 5-methylcytosine oxidases (TET proteins). Removal of CXXC5 from ES cells leads to very few changes in gene expression. CXXC5 extensively colocalizes with TET1 and TET2 at CpG islands. CXXC5 inactivation leads to a substantial reduction of DNA methylation levels that affects all genomic compartments including genic and intergenic regions and CpG island shores. We propose a model in which CXXC5 serves as an anchor for TET proteins at CpG islands. In the absence of CXXC5, the 5-methylcytosine oxidases become dislodged from CpG islands and are enabled to induce genome-scale DNA demethylation. Thus, CXXC5 serves as a stabilizer of DNA methylation patterns.

Aim: To investigate DNA methylation levels of a panel of genes in thymic epithelial tumors (TETs).Materials & methods: We selected 15 genes among the most promising epigenetic biomarkers of TETs and evaluated their methylation levels in 71 TET samples.Results: thymic carcinomas (TCs) showed hypermethylation of GHSR and ELF3 genes and reduced IL1RN methylation levels compared with thymomas (TMs) and healthy thymic tissues. RAG1 was hypomethylated in TMs compared with healthy thymic tissues. No difference in the methylation levels of the investigated genes was seen among TM stages and subtypes. No changes in blood methylation levels of the investigated genes were seen among TET subtypes.Conclusion: The present study confirms GHSR, ELF3, IL1RN and RAG1 as TET epigenetic biomarkers.

Histone deacetylase 3 (HDAC3) is a critical regulator of gene expression, influencing a variety of cellular processes in the central nervous system. As such, dysfunction of this enzyme may serve as a key driver in the pathophysiology of various neuropsychiatric disorders and neurodegenerative diseases. HDAC3 plays a crucial role in regulating neuroinflammation, and is now widely recognized as a major contributor to neurological conditions, as well as in promoting neuroprotective recovery following brain injury, hemorrhage and stroke. Emerging evidence suggests that pharmacological inhibition of HDAC3 can mitigate behavioral and neuroimmune deficits in various brain diseases and disorders, offering a promising therapeutic strategy. Understanding HDAC3 in the healthy brain lays the necessary foundation to define and resolve its dysfunction in a disease state. This review explores the mechanisms of HDAC3 in various cell types and its involvement in disease pathology, emphasizing the potential of HDAC3 inhibition to address neuroimmune, gene expression and behavioral deficits in a range of neurodegenerative and neuropsychiatric conditions.

nc886 is a regulatory noncoding RNA that is transcribed by RNA polymerase III (Pol III), is variably expressed in different biological contexts, and plays roles in inflammation and cancer. Epigenetic mechanisms play an intriguing role in regulating nc886 expression. As a maternally imprinted gene and metastable epiallele, nc866 exhibits polymorphic imprinting, with a methylation status that is influenced by environmental and biological factors. Consequently, the promoter DNA methylation status and the different resulting RNA expression levels of nc886 are associated with physiological and pathological conditions. In this review, we summarize the literature and explore the significance in relation to diverse roles of nc886.

Our understanding of the origins of noncommunicable diseases has evolved over the years with greater consideration given to the lasting influence exposures and experiences during the preconceptional and prenatal periods can have. Research highlights the associations of parental exposures (e.g., diet, obesity, gestational diabetes, lipid profile, toxic exposures and microbiome) with the infant/fetal methylome and suggest associations with infant, child and/or adolescent chronic health outcomes. Thus, epigenetics and specifically cord blood DNA methylation may have utility as biomarkers for disease risk identification and stratification in pediatrics. However, for cord blood DNA methylation analyses to be leveraged as biomarkers of disease risk in pediatric clinical practice, the results must be replicable, validated and clinically meaningful. Challenges and opportunities to this prospect are herein discussed.

Aim: DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori) infection, while increasing evidence indicated involvement of other microbes reside in gastric mucosa during gastric tumorigenesis. We investigated bacterial communities in the gastric mucosa accompanied with H. pylori related methylation anomaly.Materials & methods: Gastric mucosa samples from antrum were obtained from 182 cancer-free patients. Bacterial communities were evaluated using 16S rRNA sequencing. The result was correlated with H. pylori related promoter CpG island (CGI) methylation of five genes (IGF2, SLC16A12, SOX11, P2RX7 and MYOD1), LINE1 hypomethylation and telomere length.Results & conclusion: We showed correlation between lower bacterial alpha diversity and higher CGI methylation. Multivariate analysis demonstrated older age (t = 3.46, p = 0.0007), H. pylori infection (t = 9.99, p < 0.0001) and lower bacterial alfa diversity (Shannon index: t = -2.34, p = 0.02) were significantly associated with CGI hypermethylation. In genus or family levels, increased abundance of Helicobacter was associated with hyper CGI methylation with strongest correlation, while decreased abundance of four bacteria (Intrasporangiaceae family, Macellibacteroides, Peptostreptococcus and Dietziaceae family) was also associated with hyper CGI methylation. Our findings suggest the potential correlation between CGI methylation induction and lower bacterial alpha diversity in the gastric mucosa accompanied by H. pylori infection.

Aim: To assess the associations between genome-wide DNA methylation (DNAm) and glucose metabolism among a Chinese population, in particular the multisite correlation. Materials & methods: Epigenome-wide associations with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were analyzed among 100 Shanghai monozygotic (MZ) twin pairs using the Infinium HumanMethylationEPIC v2.0 BeadChip. We conducted a Pearson's correlation test, hierarchical cluster and pairwise analysis to examine the differential methylation patterns from clusters. Results: Cg01358804 (TXNIP) was identified as the most significant site associated with FPG and HbA1c. Two clusters with hypermethylated and hypomethylated patterns were observed for both FPG and HbA1c. Conclusion: Differential methylation patterns from clusters may provide new clues for epigenetic changes and biological mechanisms in glucose metabolism.

Objective: To elucidate the role of the competitive endogenous RNA (ceRNA) network in immune infiltration of diabetic retinopathy (DR). Methods: We obtained differentially expressed (DE) circRNAs, miRNAs and mRNAs from the Gene Expression Omnibus database. Then, we identified immune infiltration by CIBERSORT and single-sample gene set enrichment analysis and discovered co-expression genes by weighted gene co-expression network analysis. Furthermore, STAT1-mediated Th1 differentiation was determined in DR cell models, DR patients and DR mouse models. Results: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 was involved in immune infiltration of Th1 cells. Aberrant expression of the ceRNA network and STAT1-mediated Th1 differentiation was thus verified in vitro and in vivo. Conclusion: hsa_circ_0087100/hsa-miR-6743-5p/STAT1 may affect Th1 cell differentiation in DR.

Aim: To elucidate the epigenetic consequences of DNA methylation in healthspan termination (HST), considering the current limited understanding. Materials & methods: Genetically predicted DNA methylation models were established (n = 2478). These models were applied to genome-wide association study data on HST. Then, a poly-methylation risk score (PMRS) was established in 241,008 individuals from the UK Biobank. Results: Of the 63,046 CpGs from the prediction models, 13 novel CpGs were associated with HST. Furthermore, people with high PMRSs showed higher HST risk (hazard ratio: 1.18; 95% CI: 1.13-1.25). Conclusion: The study indicates that DNA methylation may influence HST by regulating the expression of genes (e.g., PRMT6, CTSK). PMRSs have a promising application in discriminating subpopulations to facilitate early prevention.