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Swiss Medical Weekly 2013DNA methylation, the addition of a methyl group to cytosines and adenosines, regulates gene expression on a level that is usually referred to as epigenetic, that is,... (Review)
Review
DNA methylation, the addition of a methyl group to cytosines and adenosines, regulates gene expression on a level that is usually referred to as epigenetic, that is, stably maintained during cell divisions. In humans, aberrant DNA methylation is associated with several malignancies, including cancer and so-called imprinting disorders, making it an attractive target for diagnostic purposes. Here we give a brief introduction to the biology of DNA methylation and present the use of methylation biomarkers in laboratory medicine. DNA methylation assays have become the standard procedure in the diagnosis of imprinting disorders, and they are about to shift cancer diagnostics and prognostics to the next level of molecular medicine. However, there is evidence of problems associated with the introduction of such cancer assays in routine diagnostics. We review several assays that have been proposed for DNA methylation analysis. The assays presented analyse the methylation status of single loci and are based either on a bisulphite-treatment or on methylation-sensitive restriction of the DNA under investigation.
Topics: DNA; DNA Methylation; Epigenesis, Genetic; Genomic Imprinting; Humans; Neoplasms; Polymerase Chain Reaction; Sulfites
PubMed: 23740463
DOI: 10.4414/smw.2013.13799 -
Nature Reviews. Rheumatology Feb 2014Several advances in 2013 have improved our understanding of how epigenetic mechanisms affect autoimmune disorders. Many new insights were made into the regulation of... (Review)
Review
Several advances in 2013 have improved our understanding of how epigenetic mechanisms affect autoimmune disorders. Many new insights were made into the regulation of gene expression by DNA methylation in systemic lupus erythematosus. For rheumatoid arthritis, complex interrelationships between DNA methylation and microRNAs in regulating gene expression were described.
Topics: Autoimmunity; DNA Methylation; Epigenomics; Gene Expression Regulation; Humans; MicroRNAs; Protein Phosphatase 2
PubMed: 24418763
DOI: 10.1038/nrrheum.2013.211 -
Trends in Neurosciences Jan 2013DNA methylation was once considered to be a static epigenetic modification whose primary function was restricted to directing the development of cellular phenotype.... (Review)
Review
DNA methylation was once considered to be a static epigenetic modification whose primary function was restricted to directing the development of cellular phenotype. However, it is now evident that the methylome is dynamically regulated across the lifespan: during development as a putative mechanism by which early experience leaves a lasting signature on the genome and during adulthood as a function of behavioral adaptation. Here, we propose that experience-dependent variations in DNA methylation, particularly within the context of learning and memory, represent a form of genomic metaplasticity that serves to prime the transcriptional response to later learning-related stimuli and neuronal reactivation.
Topics: Adaptation, Physiological; Animals; Brain; DNA Methylation; Genomics; Humans; Learning; Memory
PubMed: 23041052
DOI: 10.1016/j.tins.2012.09.003 -
Seminars in Cell & Developmental Biology Jul 2022Inherited epigenetic information has been observed to regulate a variety of complex organismal phenotypes across diverse taxa of life. This continually expanding body of... (Review)
Review
Inherited epigenetic information has been observed to regulate a variety of complex organismal phenotypes across diverse taxa of life. This continually expanding body of literature suggests that epigenetic inheritance plays a significant, and potentially fundamental, role in inheritance. Despite the important role these types of effects play in biology, the molecular mediators of this non-genetic transmission of information are just now beginning to be deciphered. Here we provide an intellectual framework for interpreting these findings and how they can interact with each other. We also define the different types of mechanisms that have been found to mediate epigenetic inheritance and to regulate whether epigenetic information persists for one or many generations. The field of epigenetic inheritance is entering an exciting phase, in which we are beginning to understand the mechanisms by which non-genetic information is transmitted to, and deciphered by, subsequent generations to maintain essential environmental information without permanently altering the genetic code. A more complete understanding of how and when epigenetic inheritance occurs will advance our understanding of numerous different aspects of biology ranging from how organisms cope with changing environments to human pathologies influenced by a parent's environment.
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Heredity; Inheritance Patterns; Phenotype
PubMed: 34426067
DOI: 10.1016/j.semcdb.2021.08.006 -
Cell Death and Differentiation Jun 2023Historical and demographical human cohorts of populations exposed to famine, as well as animal studies, revealed that exposure to food deprivation is associated to... (Review)
Review
Historical and demographical human cohorts of populations exposed to famine, as well as animal studies, revealed that exposure to food deprivation is associated to lasting health-related effects for the exposed individuals, as well as transgenerational effects in their offspring that affect their diseases' risk and overall longevity. Autophagy, an evolutionary conserved catabolic process, serves as cellular response to cope with nutrient starvation, allowing the mobilization of an internal source of stored nutrients and the production of energy. We review the evidence obtained in multiple model organisms that support the idea that autophagy induction, including through dietary regimes based on reduced food intake, is in fact associated to improved health span and extended lifespan. Thereafter, we expose autophagy-induced chromatin remodeling, such as DNA methylation and histone posttranslational modifications that are known heritable epigenetic marks, as a plausible mechanism for transgenerational epigenetic inheritance of hunger.
Topics: Animals; Humans; Epigenesis, Genetic; Epigenetic Memory; DNA Methylation; Fasting; Autophagy
PubMed: 37031275
DOI: 10.1038/s41418-023-01159-4 -
Development (Cambridge, England) Dec 2022DNA methylation is a highly conserved epigenetic modification that plays essential roles in mammalian gene regulation, genome stability and development. Despite being... (Review)
Review
DNA methylation is a highly conserved epigenetic modification that plays essential roles in mammalian gene regulation, genome stability and development. Despite being primarily considered a stable and heritable epigenetic silencing mechanism at heterochromatic and repetitive regions, whole genome methylome analysis reveals that DNA methylation can be highly cell-type specific and dynamic within proximal and distal gene regulatory elements during early embryonic development, stem cell differentiation and reprogramming, and tissue maturation. In this Review, we focus on the mechanisms and functions of regulated DNA methylation and demethylation, highlighting how these dynamics, together with crosstalk between DNA methylation and histone modifications at distinct regulatory regions, contribute to mammalian development and tissue maturation. We also discuss how recent technological advances in single-cell and long-read methylome sequencing, along with targeted epigenome-editing, are enabling unprecedented high-resolution and mechanistic dissection of DNA methylome dynamics.
Topics: Animals; Epigenome; DNA Methylation; Epigenesis, Genetic; Histone Code; Mammals
PubMed: 36519514
DOI: 10.1242/dev.182683 -
Medicine and Science in Sports and... Mar 2020DNA methylation may be one of the biological mechanisms underlying the health benefits of physical activity (PA). Our objective was to determine the association between... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
DNA methylation may be one of the biological mechanisms underlying the health benefits of physical activity (PA). Our objective was to determine the association between PA and genome-wide DNA methylation at CpG level.
METHODS
We designed a two-stage epigenome wide association study. In the discovery stage, we used 619 individuals from the REgistre GIroní del COR cohort. Next, we validated the CpG suggestively associated with PA (P < 10) in two independent populations (n = 1735 and 190, respectively). Physical activity was assessed with validated questionnaires and classified as light PA (LPA), moderate PA, vigorous PA, moderate-vigorous PA (MVPA) and total PA. We examined linear and nonlinear associations and meta-analyzed the results in the three populations. The linear associations were meta-analyzed with a fixed-effects model and the P values of the nonlinear associations with the Stouffer and Fisher methods. We established a P value threshold that fulfilled Bonferroni criteria over the number of CpG analyzed (0.05/421,940 = 1.185 × 10).
RESULTS
In the meta-analyses, two CpG sites had a statistically significant nonlinear association with MVPA. cg24155427 (P = 1.19 × 10), located in an intergenic region in chromosome 1, has been previously associated with smoking, lupus, and aging. cg09565397 (P = 1.59 × 10), located within DGAT1 in chromosome 8, which encodes an enzyme involved in triacylglycerol synthesis.
CONCLUSIONS
This population-based study identified two new, differentially methylated CpG sites with a nonlinear dose-response relationship to MVPA. These associations must be additionally validated and may be considered for further research on the biological mechanisms underlying health benefits of PA.
Topics: CpG Islands; DNA Methylation; Exercise; Genome-Wide Association Study; Humans
PubMed: 31652233
DOI: 10.1249/MSS.0000000000002174 -
Cells Jun 2020Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our...
Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our understanding of the mechanisms that contribute to sex biases in DNA methylation and gene expression, we conducted whole genome bisulfite sequencing (WGBS) as well as RNA-seq on liver samples from mice with different combinations of sex phenotype and sex-chromosome complement. We compared groups of animals with different sex phenotypes, but the same genetic sexes, and vice versa, same sex phenotypes, but different sex-chromosome complements. We also compared sex-biased DNA methylation in mouse and human livers. Our data show that sex phenotype, X-chromosome dosage, and the presence of Y chromosome shape the differences in DNA methylation between males and females. We also demonstrate that sex bias in autosomal methylation is associated with sex bias in gene expression, whereas X-chromosome dosage-dependent methylation differences are not, as expected for a dosage-compensation mechanism. Furthermore, we find partial conservation between the repertoires of mouse and human genes that are associated with sex-biased methylation, an indication that gene function is likely to be an important factor in this phenomenon.
Topics: Animals; DNA Methylation; Female; Gene Expression; Humans; Liver; Male; Phenotype; Sex Chromosomes
PubMed: 32527045
DOI: 10.3390/cells9061436 -
Cells Aug 2020Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene... (Review)
Review
Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.
Topics: DNA Methylation; Diet; Epigenomics; Humans; Mycotoxins; Neoplasms
PubMed: 32878338
DOI: 10.3390/cells9092004 -
Current Opinion in Psychology Jun 2019The recent interest in epigenetics within mental health research, from a developmental perspective, stems from the potential of DNA methylation to index both exposure to... (Review)
Review
The recent interest in epigenetics within mental health research, from a developmental perspective, stems from the potential of DNA methylation to index both exposure to adversity and vulnerability for mental health problems. Genome-wide technology has facilitated epigenome-wide association studies (EWAS), permitting 'hypothesis-free' examinations in relation to adversity and/or mental health problems. In EWAS, rather than focusing on a priori established candidate genes, the genome is screened for DNA methylation, thereby enabling a more comprehensive representation of variation associated with complex disease. Despite their 'hypothesis-free' label, however, results of EWAS are in fact conditional on several a priori hypotheses, dictated by the design of EWAS platforms as well as assumptions regarding the relevance of the biological tissue for mental health phenotypes. In this short report, we review three hidden hypotheses - and provide recommendations - that combined will be useful in designing and interpreting EWAS projects.
Topics: DNA Methylation; Epigenomics; Genome-Wide Association Study; Humans; Mental Disorders; Phenotype
PubMed: 30077874
DOI: 10.1016/j.copsyc.2018.07.009