Abstract
DNA methylation, i.e., addition of methyl group to 5′-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.
Highlights
From a chemical point of view, DNA methylation involves an addition of a methyl group to the 50 -carbon of cytosine residues in CpG dinucleotides
It is well known that hypermethylation of promoter regions could lead to transcriptional silencing of certain tumor suppressor genes and contributes to control of many regulatory proteins and enzymes
Silencing of genes involved in cell adhesion may lead to tumor aggressiveness and tumor progression [9], as was shown for CD97, CTNNA1, DLC1, and HAPLN2 genes in which hypermethylation was associated with poorer survival of patients with ovarian cancer [17]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. CGI methylation in promoters of somatic cells leads to gene silencing either by direct inhibition of transcriptional factors, or indirectly via interaction of 5mCs with methyl-CpG-binding domain (MBD) proteins that repress transcription by recruiting enzymes that deacetylate histones [5]. De novo DNA methyltransferases DNMT3a and DNMT3b create a methylation pattern on unmethylated DNA, which is maintained during subsequent cell division by DNMT1 using hemimethylated strand. These enzymes are essential in embryogenesis and their loss of function is lethal [6]. We highlight advantages, and disadvantages and challenges that each method faces
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