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.
Epigenetics, Nutrition, and Infant Health
Crystal D. Karakochuk, Kyly C. Whitfield, Tim J. Green, Klaus Kraemer in The Biology of the First 1,000 Days, 2017
DNA is tightly woven around histone proteins, forming compact complexes of DNA and protein called nucleosomes. Nucleosomes, in turn, are packed together to form chromatin. Within the nucleosomes, the histone proteins are arranged in an eight-part formation, comprising two copies each of histones H2A, H2B, H3, and H4. Histone modifications involve various posttranslational chemical alterations to the amino acids of the histone tails, including acetylation of lysine, methylation of lysine and arginine, phosphorylation of serine and threonine, and the ubiquitination of lysine [9]. There are several mechanisms by which chemical modifications of CpG sites and histones are thought to influence gene expression. The methyl group from 5-methylcytosine may block transcription factors either directly or through the recruitment of a methyl-binding protein. Alternatively, the DNMT enzymes acting on CpG sites may be physically linked to other enzymes, which bring about histone methylation and deacetylation [10]. Although chromatin remodeling is intricately controlled, a simplified summary is that the hyperacetylation of histones and hypomethylation of histones and CpGs is associated with a euchromatin (open) configuration, generally associated with facilitation of transcriptional activity. Conversely, hypoacetylation of histones and hypermethylation of histones and CpGs is associated with a heterochromatin (closed) structure and transcriptional repression [11].
The Epigenetic Role of Vitamin C in Neurological Development and Disease
Qi Chen, Margreet C.M. Vissers in Vitamin C, 2020
Cellular systems must translate a barrage of extracellular stimuli into functional changes in gene expression to survive and respond appropriately to environmental challenges. The epigenetic landscape serves to interpret these complex extracellular cues and coordinate a pertinent response by regulating relevant expression of the genome. Methylation at the C5 position of cytosine (5-methylcytosine [5mC]) is the most prevalent epigenetic modification in vertebrates and plays essential roles in development, in transcriptional regulation, and in governing cell identity [1]. These processes are facilitated by methyl-CpG-binding proteins that recognize 5mC and regulate the transcription of methylated genomic loci. The 5mC is considered a stable epigenetic hallmark of DNA and is maintained upon DNA replication by DNA methyltransferase 1 (DNMT1). Therefore, it was long believed that due to proper DNMT1 maintenance, 5mC was a permanent modification in the genome [2]. However, this poses a problem to the cell: How can the cell respond to dynamic environmental stimuli if its most prevalent epigenetic modification is irreversible? It was thus reasoned that there must be a process by which to remove this mark.
Targeted sequencing approach: Comprehensive analysis of DNA methylation and gene expression across blood and brain regions in suicide victims
Published in The World Journal of Biological Psychiatry, 2023
Katarina Kouter, Tomaž Zupanc, Alja Videtič Paska
DNA methylation is the addition of a single methyl group to a cytosine, leading to formation of 5-methylcytosine (5mC) (Prokhortchouk and Defossez 2008). The reaction is catalysed by enzymes from the DNA methyltransferases (DNMT) family, with the donor of methyl group being S-adenosyl methionine (Lyko 2018). 5mC can usually be found clustered in CpG dinucleotide motifs. CpG clusters form CpG islands (CGI) and act as regulators of gene expression in promoters and first exons (Deaton and Bird 2011). Methylation of a promotor CpG island is often associated with decreased levels of gene expression (Illingworth and Bird 2009). DNA methylation may affect gene expression following two mechanisms. First, addition of a methyl group alters DNA biophysical properties and prevents the binding of transcriptional factors to DNA (Lee et al. 2014). Second, it attracts proteins that bind to methylated DNA and thus prevent gene transcription (Du et al. 2015).
Canvassing the aetiology, prognosis and molecular signatures of obstructive sleep apnoea
Published in Biomarkers, 2019
Sartaj Khurana, Shivani Sharda, Biswajit Saha, Sachin Kumar, Randeep Guleria, Sudeep Bose
DNA methylation is one of the key epigenetic mechanisms that involve the addition of a methyl group to cytosine thereby often modifying the function of the genes. The most widely characterized DNA methylation process is the covalent addition of the methyl group at the 5-carbon of the cytosine ring resulting in 5-methylcytosine. DNA methylation regulates a variety of gene expressions associated with various cellular processes and gets dysregulated in various diseases. Very few studies till now have focused on the role of DNA methylation in OSA. OSA-related hypoxia leads to the altering in the promoter methylation of Androgen Receptor (AR), Natriuretic peptide receptor 2 (NPR2), Interleukin-1 receptor 2 (L1R2) and Speckled protein (SP140) suggesting their role in disease severity (Chen et al. 2016), whereas increased methylation of genes like Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF 1) suggested their role as crucial determinants in inflammatory responses (Kim et al. 2012). Further studies are required to elucidate the role of DNA methylation as a potential biomarker in the context of OSA.
Epigenetics, nutrition and mental health. Is there a relationship?
Published in Nutritional Neuroscience, 2018
Aaron J. Stevens, Julia J. Rucklidge, Martin A. Kennedy
Although there are many known epigenetic modifications of DNA and histones, this review will focus on the methylated form of cytosine, 5-methylcytosine (5mC). The addition of a methyl group to cytosine generates 5mC (Fig. 1), and is an important process for directing how that region of DNA will be utilized. Modification of cytosine can occur in genomic DNA when cytosine (C) occurs immediately adjacent to guanine (G), referred to as a CG dinucleotide. CG dinucleotides are recognized by DNA methyltransferase (DNMT) enzymes, which catalyse the addition of a methyl group to cytosine, converting it to 5mC (Fig. 1).21 Differences in methylation states of specific cytosine residues in the genome correlate with changes in gene expression. 5mC generally reduces the level of gene transcription by promoting formation of tightly packed DNA (chromatin) and interfering with the necessary recognition factors and proteins required for the initiation of transcription;22–27 however, it should be noted that increased methylation can also result in increased expression.28
Related Knowledge Centers
- Cytosine
- DNA
- Epigenetics
- Gene Expression
- Methyl Group
- Methylation
- Nucleoside
- Nitrogen
- Transcription
- 5-Methylcytidine