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DNA methylation
In 1942, Conrad Hal Waddington designed a study of processes in which programmed changes to the genotype, during development, led to phenotypes. Subsequently, epigenetic was shown to be hereditary and implicated in gene expression and not due to nucleotide sequence impairment (1). Currently, epigenetic is defined as being the study of stable genomic modifications that impact on gene expression and function without any alterations in the DNA sequence. Epigenetic mechanisms promote DNA methylation, histone posttranslational modifications and noncoding RNAs. This review focuses specifically on DNA methylation in relation to metabolic syndrome and oxidative stress. Most of the papers were found using the PubMedicine database with the following keywords: DNA methylation, nutrition, oxidative stress, antioxidant defense, inflammation, metabolic syndrome and fetal programming.
DNA methylation is the most studied epigenetic postreplication modification and consists of the methylation of CpG dinucleotide cytosines (2). This covalent biochemical modification to the cytosine base leads to 5-methylcytosine. In human somatic cells, methylated cytosines count for 1% of total DNA bases and affect 70-80% of all CpG dinucleotides in the genome (3). CpG dinucleotides are asymmetrically represented in the genome with CpG-poor or -rich regions. The latter are called CpG islands and cover promoter regions up to the first exons of some genes (4). They are usually nonmethylated in normal cells (5).
The enzymes implicated in this reaction are DNA methyltransferases (DNMTs) that establish and maintain DNA methylation. DNMT1, DNMT3a and DNMT3b catalyze the transfer of a methyl group from S-adenosylmethionine (SAM) to cytosine. Maintenance methylation between cell generations is very evident and carried out by DNMT1. This is the most abundant enzyme in somatic cells and it is responsible for the maintenance of DNA methylation. It is known to copy methylation patterns to the DNA strand after replicating it (6 ,7), and is required for proper embryo development, heredity and chromosome X inactivation (8 ,9). It should also be stated that DNMT3a and DNMT3b are essential for embryo development, and de novo methylation in the genome (10-12) after embryo implantation (13 ,14). Studies show that these three enzymes not only cooperate, but they also participate in de novo methylation pattern and maintenance (15 ,16).
Although DNA methylation prevents the fixation of some proteins, it is attractive for others. In...