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Epigenetics Dec 2023Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been...
Occupational characteristics have been studied as risk factors for several age-related diseases and are thought to impact the ageing process, although there has been limited empirical work demonstrating an association between adverse occupational characteristics and accelerated ageing and this prior work has yielded mixed results. We used the 2010 and 2016 waves of the Health and Retirement Study ( = 1,251) to examine the association between occupation categories and self-reported working conditions of American adults at midlife and their subsequent epigenetic ageing as measured through five epigenetic clocks: PCHorvath, PCHannum, PCPhenoAge, PCGrimAge, and DunedinPACE. We found that individuals working in sales/clerical, service, and manual work show evidence of epigenetic age acceleration compared to those working in managerial/professional jobs and that the associations were stronger with second- and third-generation clocks. Individuals reporting high stress and high physical effort at work showed evidence of epigenetic age acceleration only on PCGrimAge and DunedinPACE. Most of these associations were attenuated after adjustment for race/ethnicity, educational attainment, and lifestyle-related risk factors. Sales/clerical work remained significantly associated with PCHorvath and PCHannum, while service work remained significantly associated with PCGrimAge. The results suggest that manual work and occupational physical activity may appear to be risk factors for epigenetic age acceleration through their associations with socioeconomic status, while stress at work may be a risk factor for epigenetic age acceleration through its associations with health behaviours outside of work. Additional work is needed to understand when in the life course and the specific mechanisms through which these associations occur.
Topics: Humans; United States; Aged; DNA Methylation; Aging; Ethnicity; Epigenesis, Genetic
PubMed: 37300823
DOI: 10.1080/15592294.2023.2218763 -
Journal of the American Chemical Society Feb 2023Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that...
Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that install methyl groups onto complex molecules are highly coveted. Late-stage C-H functionalization is a particularly attractive approach, allowing chemists to bypass lengthy syntheses and facilitating the expedited synthesis of drug analogues. Herein, we disclose the direct introduction of methyl groups via C()-H functionalization of a broad array of saturated heterocycles, enabled by the merger of decatungstate photocatalysis and a unique nickel-mediated S2 bond formation. To further demonstrate its synthetic utility as a tool for late-stage functionalization, this method was applied to a range of drug molecules en route to an array of methylated drug analogues.
Topics: Methylation; Nickel
PubMed: 36696091
DOI: 10.1021/jacs.2c13396 -
Current Medicinal Chemistry 2020DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding... (Review)
Review
DNA methylation is considered as a crucial part of epigenetic modifications and a popular research topic in recent decades. It usually occurs with a methyl group adding to the fifth carbon atom of cytosine while the base sequence of DNA remains unchanged. DNA methylation has significant influences on maintaining cell functions, genetic imprinting, embryonic development and tumorigenesis procedures and hence the analysis of DNA methylation is of great medical significance. With the development of analytical techniques and further research on DNA methylation, numerous DNA methylation detection strategies based on biosensing technology have been developed to fulfill various study requirements. This article reviewed the development of electrochemistry and optical biosensing analysis of DNA methylation in recent years; in addition, we also reviewed some recent advances in the detection of DNA methylation using new techniques, such as nanopore biosensors, and highlighted the key technical and biological challenges involved in these methods. We hope this paper will provide useful information for the selection and establishment of analysis of DNA methylation.
Topics: Biosensing Techniques; DNA; DNA Methylation; Epigenesis, Genetic
PubMed: 31480993
DOI: 10.2174/0929867326666190903161750 -
International Journal of Molecular... Dec 2020Methylation is a universal biochemical process which covalently adds methyl groups to a variety of molecular targets. It plays a critical role in two major global... (Review)
Review
Methylation is a universal biochemical process which covalently adds methyl groups to a variety of molecular targets. It plays a critical role in two major global regulatory mechanisms, epigenetic modifications and imprinting, via methyl tagging on histones and DNA. During reproduction, the two genomes that unite to create a new individual are complementary but not equivalent. Methylation determines the complementary regulatory characteristics of male and female genomes. DNA methylation is executed by methyltransferases that transfer a methyl group from S-adenosylmethionine, the universal methyl donor, to cytosine residues of CG (also designated CpG). Histones are methylated mainly on lysine and arginine residues. The methylation processes regulate the main steps in reproductive physiology: gametogenesis, and early and late embryo development. A focus will be made on the impact of assisted reproductive technology and on the impact of endocrine disruptors (EDCs) via generation of oxidative stress.
Topics: Animals; DNA Methylation; Embryonic Development; Epigenesis, Genetic; Gametogenesis; Histone Code; Humans; Reproductive Techniques, Assisted
PubMed: 33297303
DOI: 10.3390/ijms21239311 -
Differential methylation pattern in pubertal girls associated with biochemical premature adrenarche.Epigenetics Dec 2023Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its...
Biochemical premature adrenarche is defined by elevated serum DHEAS [≥40 μg/dL] before age 8 y in girls. This condition is receiving more attention due to its association with obesity, hyperinsulinemia, dyslipidemia, and polycystic ovary syndrome. Nevertheless, the link between early androgen excess and these risk factors remains unknown. Epigenetic modifications, and specifically DNA methylation, have been associated with the initiation and progression of numerous disorders, including obesity and insulin resistance. The aim of this study was to determine if prepubertal androgen exposure is associated with a different methylation profile in pubertal girls. Eighty-six healthy girls were studied. At age 7 y, anthropometric measurements were begun and DHEAS levels were determined. Girls were classified into Low DHEAS (LD) [<42 μg/dL] and High DHEAS (HD) [≥42 μg/dL] groups. At Tanner stages 2 and 4 a DNA methylation microarray was performed to identify differentially methylated CpG positions (DMPs) between HD and LD groups. We observed a differential methylation pattern between pubertal girls with and without biochemical PA. Moreover, a set of DNA methylation markers, selected by the LASSO method, successfully distinguished between HD and LD girls regardless of Tanner stage. Additionally, a subset of these markers were significantly associated with glucose-related measures such as insulin level, HOMA-IR, and glycaemia. This pilot study provides evidence consistent with the hypothesis that high DHEAS concentration, or its hormonally active metabolites, may induce a unique blood methylation signature in pubertal girls, and that this methylation pattern is associated with altered glucose metabolism.
Topics: Female; Humans; Child; Adrenarche; Androgens; Pilot Projects; DNA Methylation; Dehydroepiandrosterone Sulfate; Obesity
PubMed: 37053179
DOI: 10.1080/15592294.2023.2200366 -
Ecotoxicology and Environmental Safety May 2023Accumulating evidence has demonstrated that N6-methyladenosine (mA) plays important roles in a variety of diseases. However, the specific functions of mA in CdCl-induced...
BACKGROUND
Accumulating evidence has demonstrated that N6-methyladenosine (mA) plays important roles in a variety of diseases. However, the specific functions of mA in CdCl-induced kidney injury remain unclear.
OBJECTIVE
Here, we investigate a transcriptome-wide map of mA modifications and explore the effects of mA on Cd-induced kidney injury.
MATERIALS AND METHODS
The rat kidney injury model was constructed by subcutaneous injection of CdCl (0.5, 1.0, and 2.0 mg/kg). The mA levels were measured by colorimetry. The level of expression of mA-related enzymes were detected by reverse transcription quantitative real-time PCR analysis. Transcriptome-wide mA methylome in CdCl (2.0 mg/kg) and the control group were profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq). Subsequently, the sequencing data were analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) confirmed the functional enrichment pathways of sequencing genes. In addition, a protein-protein interaction (PPI) network was applied to select hub genes.
RESULTS
The levels of mA and mA regulators (METTL3, METTL14, WTAP, YTHDF2) were significantly increased in CdCl groups. We identified a total of 2615 differentially expressed mA peaks, 868 differentially expressed genes and 200 genes with significant changes in both mA modification and gene expression levels. GO, KEGG, and GSEA analyses indicated that these genes were mainly enriched in inflammation and metabolism-related pathways such as in IL-17 signaling and fatty acid metabolism. According the result of the conjoint analysis, we identified the top ten hub genes (Fos, Hsp90aa1, Gata3, Fcer1g, Cftr, Cspg4, Atf3, Cdkn1a, Ptgs2, and Npy) which may be regulated by mA and involve in CdCl-induced kidney damage.
CONCLUSION
This study established a mA transcriptional map in a CdCl-induced kidney injury model and suggested that mA may affect CdCl induced kidney injury via regulated the inflammation and metabolism related gene.
Topics: Animals; Rats; Methylation; Cadmium; Transcriptome; Cyclic AMP Response Element-Binding Protein; Kidney
PubMed: 37054473
DOI: 10.1016/j.ecoenv.2023.114903 -
Methods in Molecular Biology (Clifton,... 2022Epigenetic modification are heritable changes in gene expression not encoded by the DNA sequence therefore playing a significant role in a broad range of biological...
Epigenetic modification are heritable changes in gene expression not encoded by the DNA sequence therefore playing a significant role in a broad range of biological processes and diseases.A key player of the epigenetic modifications is the DNA methylation, a process involving the covalent transfer of a methyl group to the C-5 position of the cytosine ring of DNA forming 5-methylcytosine (5mC), catalyzed by DNA methyltransferases. Altering the structure of the chromatin, DNA methylation has the potential to down-regulate gene expression.The here presented protocol shows a method to obtain DNA samples ready for NGS sequencing for genome-wide methylation analysis.
Topics: DNA; DNA Methylation; Epigenesis, Genetic; Epigenomics; Sequence Analysis, DNA; Sulfites
PubMed: 35727538
DOI: 10.1007/978-1-0716-2313-8_2 -
Annual Review of Public Health Apr 2022Longstanding racial/ethnic inequalities in morbidity and mortality persist in the United States. Although the determinants of health inequalities are complex, social and... (Review)
Review
Longstanding racial/ethnic inequalities in morbidity and mortality persist in the United States. Although the determinants of health inequalities are complex, social and structural factors produced by inequitable and racialized systems are recognized as contributing sources. Social epigenetics is an emerging area of research that aims to uncover biological pathways through which social experiences affect health outcomes. A growing body of literature links adverse social exposures to epigenetic mechanisms, namely DNA methylation, offering a plausible pathway through which health inequalities may arise. This review provides an overview of social epigenetics and highlights existing literature linking social exposures-i.e., psychosocial stressors, racism, discrimination, socioeconomic position, and neighborhood social environment-to DNA methylation in humans. We conclude with a discussion of social epigenetics as a mechanistic link to health inequalities and provide suggestions for future social epigenetics research on health inequalities.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Health Status Disparities; Humans; Racial Groups; United States
PubMed: 35380065
DOI: 10.1146/annurev-publhealth-052020-105613 -
Epigenetics Dec 2023N6-Methyladenosine (mA) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs....
N6-Methyladenosine (mA) plays key roles in the regulation of biological functions and cellular mechanisms for ischaemia reperfusion (IR) injury in different organs. However, little is known about the underlying mechanisms of mA-modified mRNAs in hepatic IR injury. In mouse models, liver samples were subjected to methylated RNA immunoprecipitation with high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). In total, 16917 mA peaks associated with 4098 genes were detected in the sham group, whereas 21,557 mA peaks associated with 5322 genes were detected in the IR group. There were 909 differentially expressed mA peaks, 863 differentially methylated transcripts and 516 differentially mA modification genes determined in both groups. The distribution of mA peaks was especially enriched in the coding sequence and 3'UTR. Furthermore, we identified a relationship between differentially mA methylated genes (fold change≥1.5/≤ 0.667, value≤0.05) and differentially expressed genes (fold change≥1.5 and value≤0.05) to obtain three overlapping predicted target genes (Fnip2, Phldb2, and Pcf11). Our study revealed a transcriptome-wide map of mA mRNAs in hepatic IR injury and might provide a theoretical basis for future research in terms of molecular mechanisms.
Topics: Animals; Mice; Transcriptome; DNA Methylation; Protein Processing, Post-Translational; 3' Untranslated Regions; RNA, Messenger; Reperfusion Injury
PubMed: 37066716
DOI: 10.1080/15592294.2023.2201716 -
Nature Communications May 2022Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, modified histones and DNA...
Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, modified histones and DNA methylation. Similar processes in mammals can also affect phenotype through intergenerational or trans-generational mechanisms. Here we generate a luciferase knock-in reporter mouse for the imprinted Dlk1 locus to visualise and track epigenetic fidelity across generations. Exposure to high-fat diet in pregnancy provokes sustained re-expression of the normally silent maternal Dlk1 in offspring (loss of imprinting) and increased DNA methylation at the somatic differentially methylated region (sDMR). In the next generation heterogeneous Dlk1 mis-expression is seen exclusively among animals born to F1-exposed females. Oocytes from these females show altered gene and microRNA expression without changes in DNA methylation, and correct imprinting is restored in subsequent generations. Our results illustrate how diet impacts the foetal epigenome, disturbing canonical and non-canonical imprinting mechanisms to modulate the properties of successive generations of offspring.
Topics: Animals; Biological Variation, Population; DNA Methylation; Diet, High-Fat; Epigenesis, Genetic; Female; Genomic Imprinting; Mammals; Mice; Pregnancy
PubMed: 35513363
DOI: 10.1038/s41467-022-30022-2