The Parasite's Way of Life
Eric S. Loker, Bruce V. Hofkin in Parasitology, 2023
As discussed in Chapter 2 (see Figure 2.34) histones are an especially important type of DNA-associated protein found in chromatin. The addition of methyl groups (methylation) to histone proteins is well-known as a mechanism that regulates whether associated DNA is in the heterochromatin or euchromatin form. Methyl groups are added to specific amino acid residues by a group of enzymes called methyltransferases. Histone methylation can either increase or decrease transcription of genes, depending on which amino acids in the histones are methylated and how many methyl groups are added. Methylation events that weaken chemical attractions between histones and DNA increase transcription because they enable the DNA to uncoil, allowing transcription factors and RNA polymerase to access the DNA.
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).
The Epigenetic Role of Vitamin C in Neurological Development and Disease
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
Vitamin C is a vital dietary nutrient renowned for its critical role in many physiologic processes. Its functions are broad yet crucial, serving as both a potent antioxidant and a cofactor for many enzymes essential to biological systems. Unlike most animal species, humans are unable to produce vitamin C in the liver and must acquire it through the diet, leaving the fate of many physiologic processes contingent on dietary availability. Dietary vitamin C deficiency most notably causes scurvy due to its necessity in collagen cross-linking. However, vitamin C takes part in many physiologic roles, including a newly discovered function in DNA and histone demethylation. Methylation dynamics have critical implications for health and disease, particularly in neurological development and the etiology of neuropathologies. This chapter focuses on how vitamin C influences neuronal function and how its newfound role in epigenetic regulation may have profound implications for neurological development and disease.
Epigenetic modulations in cancer: predictive biomarkers and potential targets for overcoming the resistance to topoisomerase I inhibitors
Published in Annals of Medicine, 2023
Moustafa M. Madkour, Wafaa S. Ramadan, Ekram Saleh, Raafat El-Awady
Histone methylation is the dynamic addition of one, two, or three methyl groups to specific amino acids within a histone protein. Nearly all biological processes, including DNA repair, cell cycle, stress response, transcription, development, differentiation, and aging, have been shown to be regulated by histone methylation [109]. Since abnormal histone methylation has been reported to play a causal role in tumorigenesis, it can be linked to anticancer-related drug responses [110]. Histone lysine demethylases (KDMs) are enzymes that catalyze the removal of methyl group from lysine and arginine residues on histone tails and were found to play critical roles in oncogenesis [111]. Addition of the KDM inhibitor 17-DMAG to the clinically tested combination vincristine and irinotecan significantly improved the efficacy of this combination, indicating that targeting KDM may serve as a useful approach for enhancing the response to anticancer drugs like Top I inhibitors [112].
Identification and Validation of Genes Related to RNA Methylation Modification in Diabetic Retinopathy
Published in Current Eye Research, 2023
Xue Wang, Xiaomei Li, Yuan Zong, Jian Yu, Yan Chen, Minghui Zhao, Danping Wu, Yujie Liao, Chunhui Jiang, Haohao Zhu
Epigenetics refers to a stable inheritance method that changes gene expression or gene function by regulating the interaction between the genome and the environment without changing the basic sequence of DNA, mainly including DNA methylation, histone modification, chromatin remodeling, RNA modification, etc.5 Among more than 170 kinds of RNA chemical modification methods, methylation is a main type, and 6-methyladenine (m6A) and 5-methylcytosine (m5C) are the two main modification methods of methylation.6 RNA methylation is a new type of epigenetic modification, like DNA methylation, which can regulate the post-transcriptional expression level of genes without changing the base sequence. RNA methylation mainly regulates the alternative splicing, translation efficiency and stability of mRNA by affecting the combination of mRNA and reading protein, thereby changing gene expression, and finally affecting pathological or physiological processes in organisms through changes in protein levels.7
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.
Related Knowledge Centers
- Alkylation
- Biochemistry
- Catalysis
- Chemistry
- Demethylation
- Enzyme
- Gene Expression
- Methyl Group
- Substrate
- Post-Transcriptional Modification