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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 -
Trends in Genetics : TIG Nov 2021DNA methylation is a chemical modification that defines cell type and lineage through the control of gene expression and genome stability. Disruption of DNA methylation... (Review)
Review
DNA methylation is a chemical modification that defines cell type and lineage through the control of gene expression and genome stability. Disruption of DNA methylation control mechanisms causes a variety of diseases, including cancer. Cancer cells are characterized by aberrant DNA methylation (i.e., genome-wide hypomethylation and site-specific hypermethylation), mainly targeting CpG islands in gene expression regulatory elements. In particular, the early findings that a variety of tumor suppressor genes (TSGs) are targets of DNA hypermethylation in cancer led to the proposal of a model in which aberrant DNA methylation promotes cellular oncogenesis through TSGs silencing. However, recent genome-wide analyses have revealed that this classical model needs to be reconsidered. In this review, we will discuss the molecular mechanisms of DNA methylation abnormalities in cancer as well as their therapeutic potential.
Topics: CpG Islands; DNA Methylation; Genome-Wide Association Study; Humans; Neoplasms
PubMed: 34120771
DOI: 10.1016/j.tig.2021.05.002 -
Genes Dec 2019This special issue of Genes demonstrates clearly that research in epigenetics has proceeded at a very rapid pace in the last decade. [...].
This special issue of Genes demonstrates clearly that research in epigenetics has proceeded at a very rapid pace in the last decade. [...].
Topics: DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans
PubMed: 31878110
DOI: 10.3390/genes11010023 -
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 -
Cells Oct 2022DNA methylation is critical for the normal development and functioning of the human brain, such as the proliferation and differentiation of neural stem cells, synaptic... (Review)
Review
DNA methylation is critical for the normal development and functioning of the human brain, such as the proliferation and differentiation of neural stem cells, synaptic plasticity, neuronal reparation, learning, and memory. Despite the physical stability of DNA and methylated DNA compared to other epigenetic modifications, some DNA methylation-based biomarkers have translated into clinical practice. Increasing reports indicate a strong association between DNA methylation profiles and various clinical outcomes in neurological diseases, making DNA methylation profiles valuable as novel clinical markers. In this review, we aim to discuss the latest evidence concerning DNA methylation alterations in the development of neurodegenerative, neurodevelopmental, and neuropsychiatric diseases. We also highlighted the relationship of DNA methylation alterations with the disease progression and outcome in many neurological diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and autism.
Topics: Humans; DNA Methylation; Neurodegenerative Diseases; Epigenesis, Genetic; DNA; Alzheimer Disease
PubMed: 36359835
DOI: 10.3390/cells11213439 -
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 -
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