Molecular Biology
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
A gene is a region of the chromosomal DNA that produces a functional ribonucleic acid molecule (RNA). It comprises regulatory DNA sequences that determine when and in which cell types that gene is expressed, exons that are coding sequences and interspersed introns that are non-coding DNA sequences. These regulatory sequences often consist of CpG islands, short stretches of DNA rich in dinucleotides of cytosine and guanine. The methylation status of these CpG islands determines whether that gene is expressed in a particular cell or tissue, being unmethylated in tissues where the genes are expressed. As will be discussed later, aberration of this control is one of the mechanisms of tumour suppressor gene inactivation. However, these same genes can also be regulated by proteins that recognize methylated sequences called histones2 and these in turn can be regulated by polycomb genes such as BMI1.3 Transcription is the intra-nuclear process driven by RNA polymerase whereby one of the two DNA strands acts as a template for the synthesis of a single RNA strand which is complementary to the DNA, except that uracil replaces thymine in RNA. This primary RNA transcript then undergoes post-transcriptional processing, or splicing.4 Traditional dogma held that one gene produces one protein and therefore splicing was considered to occur simply in order to remove the non-coding intronic sequences, producing messenger RNA (mRNA). It is now known that by ‘alternative splicing’, one gene can result in the production of several different but often related proteins in different tissues.5
Genetics and exercise: an introduction
Adam P. Sharples, James P. Morton, Henning Wackerhage in Molecular Exercise Physiology, 2022
You will have probably heard the term epigenetics. What is it? Epigenetics means changes in gene expression that are due to chemical modifications of the DNA or of histones that are not due to variations in the DNA sequence (17). There are two main categories of epigenetic chemical reactions: the methylation of DNA and the addition of small chemical groups such as acetyl group to histones (Figure 3.11). DNA methylation refers to the addition of a CH3 (i.e. methyl) group to a cytosine (C) that is followed by a guanine (G) in the same strand. This is referred to as a CpG where the “p” stands for the phosphate that connects two bases in the same strand. In contrast, CG refers to a C in one strand pairing with a G in the other strand. Regions with many methylated cytosines are also known as CpG islands. CpG islands are present across the whole genome but are often concentrated in promoter regions of genes.
The Precision Medicine Approach in Oncology
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
CpG islands are located at the 5’-end of genes and occupy around 60% of human gene promoters. Although the majority of CpG sites in the genome are methylated in normal cells, most of the CpG islands remain un-methylated during differentiation and development, as presumably more gene expression occurs during differentiation and development but relatively less gene expression occurs in mature healthy cells. The reduction or ablation of gene expression by DNA methylation is thought to be due to a steric effect which prevents recruitment of regulatory proteins including transcription factors to the DNA. The methylation patterns in the genome are created and maintained by methyltransferase enzymes which transfer methyl groups to DNA bases or proteins such as histones. Methylated bases have also been shown to provide preferred binding sites for methyl-binding domain proteins which are known to repress gene expression through interactions with histone deacetylases (HDACs). In addition to cancer (i.e. carcinogenesis), DNA methylation has also been shown to be associated with a number of key biological processes including genomic imprinting, X-chromosome inactivation, repetitive elements repression, and aging.
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].
The role of epigenetics in the development of childhood asthma
Published in Expert Review of Clinical Immunology, 2019
Cancan Qi, Cheng-Jian Xu, Gerard H. Koppelman
DNA methylation has a close relationship with gene expression, and this correlation can be assessed by expression quantitative trait methylation (eQTM) analysis. In cancer research, when the CpG island is located on the promoter region of a gene, high methylation (hypermethylation) typically leads to transcriptional silencing of tumor suppressor genes. However, about half of the CpG islands are located in gene body or intergenic region rather than promoters, which also play a role in regulation of gene expression such as regulating noncoding RNAs [15]. The relationship between DNA methylation and gene expression in complex disease can be more complex than that in cancer. For example, DNA methylation is not always negatively correlated with gene expression, and DNA methylation changes may be a consequence rather than cause of changes in gene expression.
The role of claudin-4 in the development of gastric cancer
Published in Scandinavian Journal of Gastroenterology, 2020
CpG island hypermethylation could lead to the silencing of some genes in early gastric tumorigenesis and GC [24]. Aberrant methylation was found in gastric epithelia in GC [25]. CpG island hypermethylation of cancer-related genes correlated with H. pylori in gastric carcinogenesis [26]. Claudin-4 expression in multistep GC progression was correlated by promoter DNA hypomethylation. Moreover, claudin-4 overexpression was associated with DNA hypomethylation in GC, and decreased claudin-4 expression was related to increased DNA methylation during advanced GC [27]. Detection of aberrant methylation is a clinical method to estimate high-risk groups, identify gastric carcinogenesis, and analyse prognosis [28]. DNA methylation status was assessed using methylation-specific polymerase chain reaction (PCR). In claudin-4-repressed cells, claudin-4 was highly expressed in the context of low DNA methylation. The relationship between DNA methylation and claudin-4 expression in gastric tissues, including normal stomach, intestinal metaplasia (IM) and gastric carcinoma, was also studied. The association between claudin-4 and DNA methylation in GC was also demonstrated through cell experiments and clinical sample tests.
Related Knowledge Centers
- Cytosine
- Directionality
- DNA
- DNA Methylation
- DNA Sequencing
- Enzyme
- Nucleotide
- Guanine
- Base Pair
- 5-Methylcytosine