Basic Principles of Epigenetics

There are approximately 23,000 genes in the genomic make-up of humans that are expressed in distinct cells at a given time (Venkatachalam, 2014). The expression of these genes by cells is managed through wrapping around groups (octamers) of globular histone proteins to form nucleosomes (Nestler, 2014). The nucleosomes are further organized into chromatins. Changes that occur in the chromatins determine the gene expression, which is the switching off of a gene (when the chromatin is condensed/silent) or switching it on when chromatin is in a relaxed state (Nestler, 2014). The dynamics of chromatin are enhanced by a controlled reversible mechanism of DNA methylation and histone modification. These two processes are enzyme based, with DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histones acetylases, histone methyltransferases and methyl-binding domain protein (MECP₂) playing vital roles (Yedery & Jerse, 2015). Methylation of DNA involves the insertion of a methyl group to 5’-position of cytosine within CpG (cytosine/guanine) pairs. S-adenosylmethionine serves as the methyl donor.

The large number of 5’-methylcytosine in mammalian DNA is found in 5’-CpG-3’ dinucleotides. Methylation may also occur in non-CpG sequences, but at relative low frequencies (Nikolova, & Hariri, 2015). Histone proteins coordinate the organization of DNA and expression of genes. Histone-modifying enzymes ensure that a receptive DNA is either a candidate for silencing or transcription. Large numbers of acetylated histones and unmethylated DNA are found in the active sites of chromatin while methylated DNA and deacetylated histone proteins are found in the silent regions of chromatin (Meissner & Walter, 2013). DNA is normally tagged with a special epigenetics “tag” that confers a special quality for gene activation or silencing. These reversible modifications of DNA and histone proteins necessitate the expression of specific genes depending on precise developmental or biochemical signals such as hormonal levels, dietary constituents and drug exposure (Lucassen et al., 2013).