Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
In summary, the profile of DNA methylation and chemical modification of histone proteins constitutes the epigenome. Epigenetic modifications can occur at all ages as a result of exposure to environmental factors, such as nutrients, cellular insults and stress. The research on whether acute exercise, exercise training or inactivity are stimuli that can trigger epigenetic events is discussed later in this book (Chapter 6). Retained epigenetic modifications to DNA in skeletal muscle tissue have been identified following exercise training, even after a period of detraining, and therefore a so-called epigenetic memory or “epi-memory” of prior exercise has been proposed. Epigenetics of exercise and muscle “memory” are also discussed in detail later in this book (Chapter 6).
Epigenetics from Oocytes to Embryos
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
As a stable epigenetic mark that is heritable through cell division, 5mC is not only an important component of maintaining cell identity but is essential for genome stability. However, the epigenome, including global DNA methylation, needs to be reprogrammed to allow for the progeny to develop. There are two waves of demethylation and subsequent remethylation that occur during mammalian development (Figure 9.1a). The first occurs during germ cell development and the other immediately after fertilization to ensure a pluripotent state. Both sperm and oocytes are considered to be the most terminally differentiated cell types of the body, and the associated epigenetic signatures of these haploid cells need to be erased to gain totipotency.10 Key events for embryonic reprogramming include the erasure of most 5mC marks inherited from the gametes, with the exception of imprinted loci and some retrotransposon sequences,11 and the establishment of embryonic methylation patterns during the processes of blastocyst implantation.12
DNA methylation analysis using bisulfite sequencing data
Altuna Akalin in Computational Genomics with R, 2020
The epigenome consists of chemical modifications of DNA and histones. These modifications are shown to be associated with gene regulation in various settings (see Chapter 1 for an intro). These modifications in turn have specific importance for cell type identification. There are many different ways of measuring such modifications. We have shown how histone modifications can be measured in a genome-wide manner in Chapter 9 using ChIP-seq. In this chapter we will focus on the analysis of DNA methylation data using data from a technique called bisulfite sequencing (BS-seq). We will introduce how to process data and data quality checks, as well as statistical analysis relevant for BS-seq data.
Ankylosing Spondylitis Patients Display Aberrant ERAP1 Gene DNA Methylation and Expression
Published in Immunological Investigations, 2022
Yubo Ma, Dazhi Fan, Shanshan Xu, Jixiang Deng, Xing Gao, Shiyang Guan, Xu Zhang, Faming Pan
DNA methylation is the most commonly reported epigenetic modification that plays a pivotal role in many life courses through programmed gene expression regulation in the genome (Chater-Diehl et al. 2021). DNA methylation is the addition of a methyl group to 5ʹ position of a cytosine DNA base in the middle of cytosine-guanine dinucleotide (CpG) (Zhu et al. 2016). The abnormal DNA methylation in the gene promoter is generally associated with transcriptional silencing and may be associated with multiple diseases (Jones et al. 2016; Zhong et al. 2016). An increasing number of epigenome-wide association studies (EWAS) indicated that DNA methylation participates in the pathogenesis of rheumatic diseases, such as systematic lupus erythematosus, rheumatoid arthritis, and AS (Hao et al. 2017; Imgenberg-Kreuz et al. 2018; Joseph et al. 2019; Webster et al. 2018; Zhu et al. 2019). A recent EWAS has identified 1915 altered DNA methylation loci in AS. Moreover, candidate gene studies also reported abnormal methylation loci in AS patients. Methylation of SOCS-1 gene was detected in the serum of HLA-B27 positive AS patients but not B27 positive controls, and it was significantly associated with higher serum cytokines and severe clinical manifestations in AS patients (Lai et al. 2014). DNMT1 and BCL11B genes were also reported to be hypermethylated in AS patients, and their expression levels were decreased (Aslani et al. 2016; Karami et al. 2017). Nevertheless, current studies focusing on DNA methylation in AS patients are still scarce and urgent.
Epigenetic regulation in Alzheimer’s disease: is it a potential therapeutic target?
Published in Expert Opinion on Therapeutic Targets, 2021
Epigenetic therapy consists of the use of drugs or other epigenome-influencing techniques to alter gene expression levels and treat medical conditions, and primarily involves inhibitors of enzymes that catalyze DNA methylation and histone tail modifications for the treatment of human cancers [9]. However, epigenetic therapy is largely investigated in animal models, cell culture models, and clinical trials of other diseases than cancer, including neurodegenerative disorders [10]. This article examines the epigenetic modifications observed in AD tissues, and particularly the changes in DNA methylation and histone tail modifications, discussing their role as potential therapeutic targets. The relevant articles discussed in the manuscript have been retrieved through a PubMed search between 2003 and 2021, including the terms ‘Alzheimer’s disease’ and ‘DNA methylation’, ‘histone tail modifications’, ‘epigenetics’, ‘epigenome-wide’, ‘whole-methylation analysis’, ‘epigenetic drugs’, ‘S-adenosylmethionine’, ‘inhibitors of histone deacetylases’, ‘inhibitors of DNA methyltransferases’, ‘animal models’, ‘epigenetic therapy’.
Targeting epigenetic regulators in the treatment of T-cell lymphoma
Published in Expert Review of Hematology, 2020
Finally, the clinical application of both new drugs and new combinations will be facilitated by predictive biomarkers that help identify patients most likely to respond to epigenetic-modifying agents, and by monitoring biomarkers that help gauge the efficacy of therapy in real time. Extensive correlative studies should be performed in clinical trials involving epigenetic-modifying agents whenever feasible, so that such biomarkers can be identified and also so that drugs that demonstrate a high degree of efficacy in a relatively small fraction of patients can be pursued using biomarker-guided approaches, potentially with accompanying development of companion diagnostics, rather than assessed only based on cohort-wide responses. Advances in the understanding of the epigenome and high-throughput approaches to characterize it in clinical samples and experimental models are facilitating this biomarker discovery. In addition to base-level, feature-level, or gene-level alterations, the areas of three-dimensional chromatin configuration and telomere science are rapidly expanding to afford new insights into potential targets for future novel agents.
Related Knowledge Centers
- DNA
- DNA Methylation
- Epigenetics
- Genome
- Histone
- Transposable Element
- Neoplasm
- Cancer
- Chromatin
- DNA
- Transgenerational Epigenetic Inheritance
- DNA Methylation