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Trends in Genetics : TIG Jul 2022In 1925, 5-methylcytosine was first reported in bacteria. However, its biological importance was not intuitive for several decades. After this initial lag, the... (Review)
Review
In 1925, 5-methylcytosine was first reported in bacteria. However, its biological importance was not intuitive for several decades. After this initial lag, the ubiquitous presence of this methylated base emerged across all domains of life and revealed a range of essential biological functions. Today, we are armed with the knowledge of the key factors that establish, maintain, and remove DNA methylation and have access to a staggering and rapidly growing number of base-resolution methylation maps. Despite this, several fundamental details about the precise role and interpretation of DNA methylation patterns remain under investigation. Here, we review the field of DNA methylation from its beginning to present day, with an emphasis on findings in mammalian systems, and point the reader to select experiments that form the foundation of this field.
Topics: 5-Methylcytosine; Animals; DNA Methylation; Mammals
PubMed: 35504755
DOI: 10.1016/j.tig.2022.03.010 -
Nature Reviews. Genetics Jun 2018Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not... (Review)
Review
Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?
Topics: Aging; Animals; DNA Methylation; Epigenesis, Genetic; Humans
PubMed: 29643443
DOI: 10.1038/s41576-018-0004-3 -
Ageing Research Reviews Nov 2022As a complicated process, aging is characterized by various changes at the cellular, subcellular and nuclear levels, one of which is epigenetic aging. With increasing... (Review)
Review
As a complicated process, aging is characterized by various changes at the cellular, subcellular and nuclear levels, one of which is epigenetic aging. With increasing awareness of the critical role that epigenetic alternations play in aging, DNA methylation patterns have been employed as a measure of biological age, currently referred to as the epigenetic clock. This review provides a comprehensive overview of the epigenetic clock as a biomarker of aging and a useful tool to manage healthy aging. In this burgeoning scientific field, various kinds of epigenetic clocks continue to emerge, including Horvath's clock, Hannum's clock, DNA PhenoAge, and DNA GrimAge. We hereby present the most classic epigenetic clocks, as well as their differences. Correlations of epigenetic age with morbidity, mortality and other factors suggest the potential of epigenetic clocks for risk prediction and identification in the context of aging. In particular, we summarize studies on promising age-reversing interventions, with epigenetic clocks employed as a practical tool in the efficacy evaluation. We also discuss how the lack of higher-quality information poses a major challenge, and offer some suggestions to address existing obstacles. Hopefully, our review will help provide an appropriate understanding of the epigenetic clocks, thereby enabling novel insights into the aging process and how it can be manipulated to promote healthy aging.
Topics: Aging; Biomarkers; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 36206857
DOI: 10.1016/j.arr.2022.101743 -
International Journal of Biological... 2015DNA methylation regulates many cellular processes, including embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting and... (Review)
Review
DNA methylation regulates many cellular processes, including embryonic development, transcription, chromatin structure, X-chromosome inactivation, genomic imprinting and chromosome stability. DNA methyltransferases establish and maintain the presence of 5-methylcytosine (5mC), and ten-eleven translocation cytosine dioxygenases (TETs) oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), which can be removed by base excision repair (BER) proteins. Multiple forms of DNA methylation are recognised by methyl-CpG binding proteins (MeCPs), which play vital roles in chromatin-based transcriptional regulation, DNA repair and replication. Accordingly, defects in DNA methylation and its mediators may cause silencing of tumour suppressor genes and misregulation of multiple cell cycles, DNA repair and chromosome stability genes, and hence contribute to genome instability in various human diseases, including cancer. Thus, understanding functional genetic mutations and aberrant expression of these DNA methylation mediators is critical to deciphering the crosstalk between concurrent genetic and epigenetic alterations in specific cancer types and to the development of new therapeutic strategies.
Topics: Carcinogenesis; DNA Methylation; Epigenomics; Humans; Neoplasms
PubMed: 25892967
DOI: 10.7150/ijbs.11218 -
Essays in Biochemistry Dec 2019DNA methylation is an epigenetic mark involved in regulating genome function and is critical for normal development in mammals. It has been observed that the... (Review)
Review
DNA methylation is an epigenetic mark involved in regulating genome function and is critical for normal development in mammals. It has been observed that the developmental environment can lead to permanent changes in gene expression and DNA methylation, at least at 'metastable epialleles'. These are defined as regions of the genome that show a variable epigenetic state that is established early in development and maintained through subsequent cell divisions. However, the majority of the known genome does not behave in this manner. Here, we use the developmental origins of adult disease hypothesis to understand environmental epigenomics. Some challenges to studying how DNA methylation is influenced by the environment include identifying DNA methylation changes associated with an environmental exposure in tissues with a complex cellular composition and at genomic regions for which DNA methylation is dynamically regulated in a cell-type specific manner. We also offer a perspective of how emerging technologies may be useful for dissecting the functional contribution of exposure-associated epigenetic changes and highlight recent evidence that suggests that genomic regions that are absent from genome assemblies may be unappreciated hotspots for environmental modulation of the epigenetic state.
Topics: Animals; DNA; DNA Methylation; Epigenesis, Genetic; Gene-Environment Interaction; Humans
PubMed: 31782496
DOI: 10.1042/EBC20190031 -
Endocrine-related Cancer Jul 2019In recent years, cancer genomics has provided new insights into genetic alterations and signaling pathways involved in thyroid cancer. However, the picture of the... (Review)
Review
In recent years, cancer genomics has provided new insights into genetic alterations and signaling pathways involved in thyroid cancer. However, the picture of the molecular landscape is not yet complete. DNA methylation, the most widely studied epigenetic mechanism, is altered in thyroid cancer. Recent technological advances have allowed the identification of novel differentially methylated regions, methylation signatures and potential biomarkers. However, despite recent progress in cataloging methylation alterations in thyroid cancer, many questions remain unanswered. The aim of this review is to comprehensively examine the current knowledge on DNA methylation in thyroid cancer and discuss its potential clinical applications. After providing a general overview of DNA methylation and its dysregulation in cancer, we carefully describe the aberrant methylation changes in thyroid cancer and relate them to methylation patterns, global hypomethylation and gene-specific alterations. We hope this review helps to accelerate the use of the diagnostic, prognostic and therapeutic potential of DNA methylation for the benefit of thyroid cancer patients.
Topics: Antineoplastic Agents; Biomarkers, Tumor; DNA Methylation; Demethylation; Epigenome; Gene Expression Regulation, Neoplastic; Humans; Prognosis; Signal Transduction; Thyroid Neoplasms
PubMed: 31035251
DOI: 10.1530/ERC-19-0093 -
Trends in Endocrinology and Metabolism:... Jul 2020The prevalence of obesity and associated diseases has reached pandemic levels. Obesity is often associated with overnutrition and a sedentary lifestyle, but clearly... (Review)
Review
The prevalence of obesity and associated diseases has reached pandemic levels. Obesity is often associated with overnutrition and a sedentary lifestyle, but clearly other factors also increase the susceptibility of metabolic disease states. Ancestral and direct exposures to environmental toxicants and altered nutrition have been shown to increase susceptibility for obesity and metabolic dysregulation. Environmental insults can reprogram the epigenome of the germline (sperm and eggs), which transmits the susceptibility for disease to future generations through epigenetic transgenerational inheritance. In this review, we discuss current evidence and molecular mechanisms for epigenetic transgenerational inheritance of obesity susceptibility. Understanding ancestral environmental insults and epigenetic transgenerational impacts on future generations will be critical to fully understand the etiology of obesity and to develop preventative therapy options.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Male; Obesity
PubMed: 32521235
DOI: 10.1016/j.tem.2020.02.009 -
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 -
Journal of Experimental & Clinical... Mar 2022DNA methylation is one of the most important epigenetic mechanisms to regulate gene expression, which is highly dynamic during development and specifically maintained in... (Review)
Review
DNA methylation is one of the most important epigenetic mechanisms to regulate gene expression, which is highly dynamic during development and specifically maintained in somatic cells. Aberrant DNA methylation patterns are strongly associated with human diseases including cancer. How are the cell-specific DNA methylation patterns established or disturbed is a pivotal question in developmental biology and cancer epigenetics. Currently, compelling evidence has emerged that long non-coding RNA (lncRNA) mediates DNA methylation in both physiological and pathological conditions. In this review, we provide an overview of the current understanding of lncRNA-mediated DNA methylation, with emphasis on the roles of this mechanism in cancer, which to the best of our knowledge, has not been systematically summarized. In addition, we also discuss the potential clinical applications of this mechanism in RNA-targeting drug development.
Topics: DNA Methylation; Humans; Neoplasms; RNA, Long Noncoding
PubMed: 35292092
DOI: 10.1186/s13046-022-02319-z -
Nutrients Mar 2019DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in... (Review)
Review
DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.
Topics: DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Micronutrients; Neoplasms; Nutritional Status
PubMed: 30871166
DOI: 10.3390/nu11030608