Systemic Lupus Erythematosus
Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide in Clinical Innovation in Rheumatology, 2023
DNA methylation is an epigenetic mechanism where a methyl group is transferred to the fifth carbon of the cytosine pyrimidine ring and involved in cell differentiation, silencing of transposable elements, and gene imprinting. UV light, hydralazine, and procainamide can inhibit DNA methylation, inciting SLE-like disease. One of the first studies on DNA methylation showed that suppressing this process in CD4+ T cells during mitosis led to formation of autoreactive CD4+ T cells. This was backed by more studies which revealed that expression of genes suppressed by DNA methylation can lead to T cell–mediated autoreactivity.83 Studies with microarrays have shown that hypomethylation of IFN genes such as MX1, BST2, and IFI44L can lead to SLE pathogenesis.50
Mother and Embryo Cross Communication during Conception
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Histone modification is another epigenetic mechanism. Histones are basic proteins acting as spools around which DNA winds, packaging it into structural units, called nucleosomes. A histone octamer consisting of two copies of each of the four core histones (H2A, H2B, H3, and H4), around which approximately 146 bp of the DNA winds, comprises a nucleosome. It has been shown that histones are subject to numerous covalent modifications, including methylation, acetylation, phosphorylation, sumoylation, glycosylation, and ubiquitination, at specific tails of selected amino acids. A number of enzymes are involved in this process, including histone methyltransferases (HMTs), acetyltransferases (HATs), kinases, and ubiquitin ligases functioning as writers, as well as erasers, such as histone demethylases, deacetylases (HDACs), and phosphatases, capable of removing modification marks from the histone tails. These modifications impose either transcriptionally repressive or transcriptionally permissive chromatin structures. For instance, histone acetylation usually results in active genes as does the di- or trimethylation of lysine residue 4 in histone H3 (H3K4me2, H3K4me3), whereas H3K9me2/3 and H3K27me3 modifications repress gene expression. In general, unlike DNA methylation, which is believed to confer a more stable and long-term silencing mechanism, various histone modifications seem to exert short-term, flexible regulation important for the plasticity of development [140–144].
Psychiatric Disorders in Women
Michelle Tollefson, Nancy Eriksen, Neha Pathak in Improving Women's Health Across the Lifespan, 2021
Epigenetics refers to the processes and structures that regulate how DNA is packaged and transcribed within the cell. The epigenome, which consists of various chemical markers attached to genes and associated histone proteins, responds to intrinsic and extrinsic environmental factors, and causes differential expression or inactivation of genes. Therefore, the epigenome represents a mechanism by which certain pathologies may arise without the alteration of DNA itself. Growing evidence suggests that a wide variety of diseases are linked to epigenetic changes, including nearly all cancers, cognitive dysfunction, autoimmune disorders, and mental health disorders.36 It has also been found that unhealthy lifestyle behaviors may influence the onset and progression of many of these diseases through epigenetic mechanisms. On the other hand, healthy lifestyle behaviors have been shown to health-promoting gene expression through epigenetic regulation.37
Epigenetic regulation of T cell development
Published in International Reviews of Immunology, 2023
Avik Dutta, Harini Venkataganesh, Paul E. Love
Several reports suggest that polycomb group (PcG) proteins govern the H3K27 methylation mark [25] and that Polycomb repressor complex (PRC) maintains the repressive state. There are three groups of PRCs: PRC1, PRC2, and Polycomb Repressive-Deubiquitinase (PR-DUB) complex [26, 27]. Each group has individual ways of remodeling chromatin, contributing to the epigenetic repression of genes important for cell development and proliferation. The PRC1 complex, which consists of several proteins including BMI-1, Ring1, and HPH proteins, recognizes and trimethylates K27 of histone 3 (H3K27me3) and helps to maintain the repressive state. The PRC2 complex includes EZH1 (enhancer of zeste homolog 1), EZH2, EED and SUV12 and initiates early gene repression with the help of histone deacetylases (HDACs) and DNMTs [25]. The discovery of histone demethylase LSD1 (Lysine-specific histone demethylase 1 A; encoded by the KDM1A gene) advanced the field as previously it was thought that histone methylation is permanent. This discovery has contributed to a dynamic view of chromatin remodeling [23, 28]. LSD1 demethylates H3K4 and H3K9 and is found to be upregulated in many cancers including T cell acute lymphoblastic leukemia (T-ALL) [29]. Several reports have also shown that the histone H3 K27 demethylases, KDM6A (Utx) and KDM6B (Jmjd3), help to shape the chromatin architecture and regulate gene expression by removing repressive histone modifications [30].
Association between the Extent of Peripheral Blood DNA Methylation of HIF3A and Accumulation of Adiposity in community-dwelling Women: The Yakumo Study
Published in Endocrine Research, 2022
Genki Mizuno, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Ryosuke Fujii, Yoshiki Tsuboi, Atsushi Teshigawara, Itsuki Kageyama, Keisuke Osakabe, Keiko Sugimoto, Hiroaki Ishikawa, Naohiro Ichino, Yoshiji Ohta, Koji Ohashi, Shuji Hashimoto, Koji Suzuki
Lifestyle and/or environmental factors cause epigenetic alterations, which play a critical role in several health conditions such as obesity and metabolic disease.13–16 DNA methylation is an epigenetic mechanism that regulates gene expression by adding a methyl donor to cytosine to enable the regulation of transcription.17 Lifestyle factors, including dietary habits, modulate DNA methylation.18,19 Several animal20–22 and epidemiological studies23–25 have shown that environmental factors, including food intake, tobacco smoking, and alcohol consumption, cause DNA methylation in blood or tissues. Moreover, global DNA hypermethylation of leukocytes is associated with an increased risk of cardiovascular diseases in the general Japanese population.26 Thus, DNA methylation might be a novel biomarker of metabolic diseases caused by environmental factors and lifestyle.
Epigenetics in drug disposition & drug therapy: symposium report of the 24th North American meeting of the International Society for the Study of Xenobiotics (ISSX)
Published in Drug Metabolism Reviews, 2022
Benjamin J. Maldonato, Ana G. Vergara, Jaydeep Yadav, Sarah M. Glass, Erickson M. Paragas, Dongying Li, Philip Lazarus, Joseph L. McClay, Baitang Ning, Ann K. Daly, Laura E. Russell
The session chair, Ann Daly (Newcastle University, Newcastle upon Tyne, United Kingdom), recognized that although considerable progress has been made in the field, this is still a relatively poorly understood area, and that studying changes in epigenetic regulation due to disease and environmental factors are of particular importance for maximizing effective drug therapy. Drugs that epigenetically modulate gene expression, especially those relevant to oncology, are increasingly being investigated and approved, and the scientific community is just beginning to scratch the surface in terms of understanding implications on biological processes. Pharmaceutical companies have invested heavily into epigenetics research with a particular interest in oncology. However, epigenetics is also of increasing interest in disease areas outside of oncology including metabolic diseases such as metabolic-associated fatty liver disease (Bayoumi et al. 2020), central nervous system pathologies including Alzheimer’s Disease, and inflammatory diseases such as asthma (Prachayasittikul et al. 2017). The global epigenetics market was valued at $1.0 billion USD in 2020 and is projected to reach $4.1 billion USD by 2030, growing at a compound annual growth rate of 14.1% from 2021 to 2030 (Balkrishna and Sumant 2022). The major classes of epigenetic drugs currently in use are DNA methylation inhibiting drugs, bromodomain inhibitors, histone acetyltransferase inhibitors, histone deacetylase inhibitors, protein methyltransferase inhibitors, and histone methyltransferase inhibitors (Heerboth et al. 2014).
Related Knowledge Centers
- DNA Methylation
- DNA Sequencing
- Genome
- Histone
- Phenotypic Trait
- Physiology
- DNA Sequencing
- Gene
- Regulation of Gene Expression
- Cell
- Nucleic Acid Sequence
- DNA Methylation