The Role of Epigenetics in Breast Cancer: Implications for Diagnosis, Prognosis, and Treatment
Brian Leyland-Jones in Pharmacogenetics of Breast Cancer, 2020
There are distinct mechanisms that initiate and sustain epigenetic modifications (2–8). Of these, DNA methylation and posttranslational modifications of histone proteins are the best understood. DNA methylation is a covalent addition of a methyl group to DNA, usually to a cytosine located 5’ to guanasine (CpG dinucleotide). CpG dinucleotides are underrepresented in the genome, except for small clusters, referred to as CpG islands, located in or near the promoter of approximately half of all genes (1,9-11). In addition, other epigenetic modifications have recently been explored, including the Polycomb group (PcG) proteins, which repress gene function and can only be overcome by germline differentiation processes, and small noncoding RNA molecules, which regulate gene expression by targeting RNA degradation (3). Small noncoding RNA molecules have recently been found to also target gene promoters and result in transcriptional gene silencing (11,12).
Epigenetic Alterations in Alzheimer’s Disease and Its Therapeutic and Dietary Interventions
Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu in Phytomedicine and Alzheimer’s Disease, 2020
One of the best-studied epigenetic modifications is DNA methylation, which refers to the binding of a methyl group (–CH3) to the carbon in position 5 of a cytosine moiety, resulting in the formation of 5-methylcytosine (5mC). The classic functions of DNA methylation are genomic imprinting, X-chromosome inactivation in mammalian females, and gene silencing. This reaction occurs mostly at so-called CpG islands and is catalyzed by enzymes known as DNA methyltransferases (DNMTs). DNMTs are of four types, namely DNMT1, DNMT2, DNMT3a, and DNMT3b. DNA methylation appears to be frequently involved in the processes associated with both healthy and diseased aging, particularly in neurological and neurodegenerative diseases. Finally, the 5mC can be converted into 5-hydroxymethyl cytosine (5hmC), which is abundant in the brain (Tognini et al. 2015). The appropriate balance between methylated and demethylated states defines the state of health and disease.
Laboratory Molecular Methodologies to Analyze DNA Methylation
Cristina Camprubí, Joan Blanco in Epigenetics and Assisted Reproduction, 2018
DNA methylation involves the addition of a methyl group to the fifth carbon of the DNA cytosine base (C), forming 5-methyl-cytsone (5mC). This represents one of the most studied epigenetic marks, primarily due to the fact that this modification is stable in archived DNA samples. DNA methylation predominantly occurs at CpG dinucleotides (CpGs), but in certain tissues and developmental settings it can occur in non-CpG contexts (e.g., CHG and CHH, where H = A, T, C). The process of methylating CpGs is catalyzed by the DNA methyltransferases (DNMTs), of which 3 are responsible for the de novo establishment, DNMT3A and DNMT3B (1) and an active rodent-specific pseudogene, DNMT3C, which is responsible for silencing retrotransposons (2). Once present, maintenance of the methylation profile during replication is performed by DNMT1 (3). DNA methylation has been associated with a number cellular processes including X chromosome inactivation in females, genomic imprinting, retrotransposon silencing and transcriptional repression, many of which show temporal profiles, highlighted by the dynamically remodeled that occurs during distinct epigenetic reprograming events (4).
DNA methylation abnormalities in atherosclerosis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Samira Tabaei, Seyyedeh Samaneh Tabaee
DNA methylation is a process which a methyl group is added to the carbon of cytosine at 5’ position in a CpG site. Actually, methyl group is added to a cytosine-paired-with-guanine (CpG) dinucleotide sequences through DNA methylation process [21]. Furthermore, methyl group could have added to a cytosine residue which is not located adjacently to a guanine residue [22]. Most of CpG sites (more than 70%) are methylated in the genome, which are actually distributed throughout the majority of the genome including transposable elements, endogenous repeats and gene bodies. CpG islands, dense and high number of CpG sites in a short area of DNA, are mainly located at the promoter region and generally are unmethylated. The main characteristics of a CpG island are; at least 200 bp in length, GC content more than 50%, and the observed/expected ratio of CpG frequency more than 0.6 [23].
Targeting MTHFR for the treatment of migraines
Published in Expert Opinion on Therapeutic Targets, 2019
Innocenzo Rainero, Alessandro Vacca, Fausto Roveta, Flora Govone, Annalisa Gai, Elisa Rubino
In recent years, the role of epigenetics in migraine has become an emerging topic of interest [40]. Epigenetic processes are fundamental in programming cellular responses to environmental factors, and in complex disorder such as migraine could explain how endogenous and exogenous factors bidirectionally modulate the clinical characteristics of the disease. Epigenetics includes both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. DNA methylation plays important roles in many cellular processes, such as gene transcription, genomic imprinting, and X-chromosome inactivation. Previous studies highlighted the role of MTHFR gene in DNA methylation cycle, as well as in folate metabolism, and DNA stability [41]. Intriguingly, valproate, a drug currently used in migraine prophylaxis, can regulate epigenetic mechanisms inhibiting histone deacetylation as well as DNA methylation [42]. In addition, 17ß-estradiol, a well-known epigenetic modulator, may play a role in migraine pathogenesis [43]. Finally, the first epigenome-wide association study identified 62 independent differentially methylated regions involved in migraine [44]. In the coming years, the next-generation sequencing techniques as well as more accurate and precise migraine phenotyping approach are expected to further increase understanding of migraine genetics.
Impact of waterpipe and tobacco cigarette smoking on global DNA methylation and nuclear proteins genes transcription in spermatozoa: a comparative investigation
Published in Inhalation Toxicology, 2023
Mohammed M. Laqqan, Said S. Al-Ghora, Maged M. Yassin
In general, smoking has been shown to be associated with epigenetic alterations that might predispose smokers to infertility (Xia et al. 2015; Olszewska et al. 2017; Kahl et al. 2018). This includes the silencing or overexpression of genes via changing the level of DNA methylation (Gao et al. 2015). DNA methylation is a major epigenetic modification involving the addition of the CH3 group to the 5th position of the cytosine nucleotide by DNA methyltransferase (DNMTs) to form 5-methylcytosine (Rang and Boonstra 2014; Jenkins et al. 2017). DNA methylation plays a vital role in different cellular processes such as genomic imprinting, silencing of transposons, X-chromosome inactivation, and regulation of gene expression (Hackett and Surani 2013). Previous studies showed an association between the alteration in the methylation level and the gene transcription level in males suffering from infertility problems (Xia et al. 2015; Nasri et al. 2017; Laqqan and Yassin 2022). This may be explained on the basis that prolonged smoking leads to an increase in the leukocyte concentration in human semen fluid, which can potentially increase reactive oxygen species (ROS) (Agarwal et al. 2015), which has harmful effects on human spermatozoa in terms of affecting the semen parameters and altering sperm DNA methylation (Wu and Ni 2015; Aitken 2018; Parameswari and Sridharan 2021).
Related Knowledge Centers
- Adenine
- Ageing
- DNA
- Genomic Imprinting
- Methyl Group
- Transposable Element
- Promoter
- Transcription
- X-Inactivation
- Carcinogenesis