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Genes Dec 2021The pathogenesis of allergic rhinitis is associated with genetic, environmental, and epigenetic factors. Genotyping of single nucleotide polymorphisms (SNPs) is an... (Review)
Review
The pathogenesis of allergic rhinitis is associated with genetic, environmental, and epigenetic factors. Genotyping of single nucleotide polymorphisms (SNPs) is an advanced technique in the field of molecular genetics that is closely correlated with genome-wide association studies (GWASs) in large population groups with allergic diseases. Many recent studies have paid attention to the role of epigenetics, including alteration of DNA methylation, histone acetylation, and miRNA levels in the pathogenesis of allergic rhinitis. In this review article, genetics and epigenetics of allergic rhinitis, including information regarding functions and significance of previously known and newly-discovered genes, are summarized. Directions for future genetic and epigenetic studies of allergic rhinitis are also proposed.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Genetics; Genome-Wide Association Study; Humans; Polymorphism, Single Nucleotide; Rhinitis, Allergic
PubMed: 34946955
DOI: 10.3390/genes12122004 -
International Journal of Molecular... Apr 2021DNA methylation, i.e., addition of methyl group to 5'-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene... (Review)
Review
DNA methylation, i.e., addition of methyl group to 5'-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.
Topics: 5-Methylcytosine; Animals; Biosensing Techniques; DNA Methylation; Epigenesis, Genetic; Humans
PubMed: 33921911
DOI: 10.3390/ijms22084247 -
Proceedings of the National Academy of... Dec 2023Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging....
Existing single-cell bisulfite-based DNA methylation analysis is limited by low DNA recovery, and the measurement of 5hmC at single-base resolution remains challenging. Here, we present a bisulfite-free single-cell whole-genome 5mC and 5hmC profiling technique, named Cabernet, which can characterize 5mC and 5hmC at single-base resolution with high genomic coverage. Cabernet utilizes Tn5 transposome for DNA fragmentation, which enables the discrimination between different alleles for measuring hemi-methylation status. Using Cabernet, we revealed the 5mC, hemi-5mC and 5hmC dynamics during early mouse embryo development, uncovering genomic regions exclusively governed by active or passive demethylation. We show that hemi-methylation status can be used to distinguish between pre- and post-replication cells, enabling more efficient cell grouping when integrated with 5mC profiles. The property of Tn5 naturally enables Cabernet to achieve high-throughput single-cell methylome profiling, where we probed mouse cortical neurons and embryonic day 7.5 (E7.5) embryos, and constructed the library for thousands of single cells at high efficiency, demonstrating its potential for analyzing complex tissues at substantially low cost. Together, we present a way of high-throughput methylome and hydroxymethylome detection at single-cell resolution, enabling efficient analysis of the epigenetic status of biological systems with complicated nature such as neurons and cancer cells.
Topics: Animals; Mice; 5-Methylcytosine; DNA Methylation; Sulfites; Sequence Analysis, DNA; Cytosine
PubMed: 38011566
DOI: 10.1073/pnas.2310367120 -
BMC Medicine Sep 2023Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined.
METHODS
We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol-rich, low-red/processed meat Green-MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green-MED group consumed green tea (3-4 cups/day) and Mankai (Wolffia globosa strain) 500-ml green shake (+ 800 mg/day polyphenols). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight).
RESULTS
Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e - 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = - 0.41, p = 0.004 and beta = - 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = - 1.8; p = 0.061) and green tea (beta = - 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02).
CONCLUSIONS
This study showed that MED and green-MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03020186.
Topics: Humans; Adult; Middle Aged; DNA Methylation; Aging; Diet, Mediterranean; Ethnicity; Gastrointestinal Microbiome
PubMed: 37743489
DOI: 10.1186/s12916-023-03067-3 -
Roczniki Panstwowego Zakladu Higieny 2021DNA methylation is a reversible epigenetic modification that plays a crucial role in transcriptional gene silencing. Both excessive (hypermethylation) and reduced DNA...
DNA methylation is a reversible epigenetic modification that plays a crucial role in transcriptional gene silencing. Both excessive (hypermethylation) and reduced DNA methylation (hypomethylation) can contribute to the disturbance of the proper course of many important processes in the human body. The aim of the study was to discuss the relationship between methyl nutrients and the DNA methylation process in the course of selected diseases in adults. Methyl nutrients include folates (vitamin B9), riboflavin (vitamin B2), cobalamin (vitamin B12), pyridoxine (vitamin B6) and choline (vitamin B4), as well as methionine and betaine. These substances play the role of both substrates and cofactors in transformations related to one-carbon metabolism. The deficiency of methyl nutrients in the body can lead to disturbances in SAM synthesis, which is the primary donor of methyl groups in the DNA methylation process. However, the mechanism explaining the discussed relationship has not been fully explained so far. Both the concentration in the body and the intake of folate and vitamin B12 in the diet can, to some extent, have an effect on the level of DNA methylation in healthy people. In comparison, data on the effect of excessive intake of vitamin B12 in the diet on the risk of cancer development are inconsistent. An adequate betaine and choline intake in the diet might not only affect the overall improvement of the DNA methylation profile, but, to some extent, also reduce the risk of cancer, the effect of which can depend on the content of folic acid in the body. Research results on the effect of supplementation of methyl nutrients on the DNA methylation process are inconclusive. It is therefore necessary to conduct further research in this area to draw clear conclusions.
Topics: Adult; Carbon; DNA Methylation; Diet; Epigenesis, Genetic; Folic Acid; Humans; Nutrients; One-Carbon Group Transferases; Vitamin B 12; Vitamin B 6
PubMed: 34114759
DOI: 10.32394/rpzh.2021.0157 -
Proceedings of the National Academy of... Apr 2023The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy...
The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.
Topics: Female; Humans; Methylation; DNA Copy Number Variations; 5-Methylcytosine; DNA; Mutation; Neoplasms; DNA Methylation
PubMed: 37014860
DOI: 10.1073/pnas.2220704120 -
Circulation Aug 2019DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.
METHODS
Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.
RESULTS
Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.
CONCLUSION
Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.
Topics: Adult; Aged; Cohort Studies; Coronary Disease; CpG Islands; DNA Methylation; Europe; Female; Genome-Wide Association Study; Humans; Incidence; Leukocytes; Male; Middle Aged; Myocardial Infarction; Population Groups; Prognosis; Prospective Studies; Risk; United States
PubMed: 31424985
DOI: 10.1161/CIRCULATIONAHA.118.039357 -
International Journal of Molecular... Jul 2022Methyl group metabolism belongs to a relatively understudied field of research. Its importance lies in the fact that methyl group metabolic pathways are crucial for the... (Review)
Review
Methyl group metabolism belongs to a relatively understudied field of research. Its importance lies in the fact that methyl group metabolic pathways are crucial for the successful conversion of dietary nutrients into the basic building blocks to carry out any cellular methylation reaction. Methyl groups play essential roles in numerous cellular functions such as DNA methylation, nucleotide- and protein biosynthesis. Especially, DNA methylation is responsible for organizing the genome into transcriptionally silent and active regions. Ultimately, it is this proper annotation that determines the quality of expression patterns required to ensure and shape the phenotypic integrity and function of a highly specialized cell type. Life is characterized by constantly changing environmental conditions, which are addressed by changes in DNA methylation. This relationship is increasingly coming into focus as it is of fundamental importance for differentiation, aging, and cancer. The stability and permanence of these metabolic processes, fueling the supplementation of methyl groups, seem to be important criteria to prevent deficiencies and erosion of the methylome. Alterations in the metabolic processes can lead to epigenetic and genetic perturbations, causative for diverse disorders, accelerated aging, and various age-related diseases. In recent decades, the intake of methyl group compounds has changed significantly due to, e.g., environmental pollution and food additives. Based on the current knowledge, this review provides a brief overview of the highly interconnected relationship between nutrition, metabolism, changes in epigenetic modifications, cancer, and aging. One goal is to provide an impetus to additionally investigate changes in DNA methylation as a possible consequence of an impaired methyl group metabolism.
Topics: Aging; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Neoplasms
PubMed: 35955511
DOI: 10.3390/ijms23158378 -
Genes & Development Aug 2023Specialized enzymes add methyl groups to the nitrogens of the amino acid histidine, altering the chemical properties of its imidazole ring and, in turn, the function of... (Review)
Review
Specialized enzymes add methyl groups to the nitrogens of the amino acid histidine, altering the chemical properties of its imidazole ring and, in turn, the function of the modified (poly)peptide. In this issue of , Shimazu and colleagues (pp. 724-742) make the remarkable discovery that CARNMT1 acts as a dual-specificity histidine methyltransferase, modifying both the small-molecule dipeptide carnosine and a set of proteins, predominantly within RNA-binding C3H zinc finger (C3H ZF) motifs. As a result, CARNMT1 modulates the activity of its protein targets to affect RNA processing and metabolism, ultimately contributing an essential function during mammalian development.
Topics: Animals; Histidine; Methylation; Amino Acids; Methyltransferases; Organogenesis; Mammals
PubMed: 37673460
DOI: 10.1101/gad.351097.123 -
Osteoarthritis and Cartilage Feb 2021In this review, we have highlighted advances in genetics, genomics and epigenetics in the field of osteoarthritis (OA) over the past year. (Review)
Review
OBJECTIVE
In this review, we have highlighted advances in genetics, genomics and epigenetics in the field of osteoarthritis (OA) over the past year.
METHODS
A literature search was performed using PubMed and the criteria: "osteoarthritis" and one of the following terms "genetic(s), genomic(s), epigenetic(s), epigenomic(s), noncoding RNA, microRNA, long noncoding RNA, lncRNA, circular RNA, RNA sequencing, single cell sequencing, or DNA methylation between April 1, 2019 and April 30, 2020.
RESULTS
We identified 653 unique publications, many studies spanned multiple search terms. We summarized advances relating to evolutionary genetics, pain, ethnicity specific risk factors, functional studies of gene variants, and interactions between coding and non-coding RNAs in OA pathogenesis.
CONCLUSIONS
Studies have identified variants contributing to OA susceptibility, candidate biomarkers for diagnosis and prognosis, as well as promising therapeutic candidates. Validation in multiple cohorts, multi-omics strategies, and machine learning aided computational analyses have all contributed to the strength of published literature. Open access data-sets, greater sample sizes to capture broader populations and understanding disease mechanisms by investigating the interactions between multiple tissue types will further aid in progress towards understanding and curing OA.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Ethnicity; Genetic Predisposition to Disease; Genomics; Humans; MicroRNAs; Osteoarthritis; Polymorphism, Genetic; RNA, Circular; RNA, Long Noncoding
PubMed: 33227439
DOI: 10.1016/j.joca.2020.11.003