**3. Mitochondrial methylation**

than resulting in a direct disease phenotype. At this point, methylation is not considered as a mutation, despite the fact that it prevents cytosine behaviour by adding a methyl group from

The most appropriate means of this option are the CpG sequences within the DNA, which are bound to their conjugates through an enzymatic process in a stronger manner compared to the A-T pairs. This is because ApTs are bound to their complementary pairs in the corresponding chain by means of two hydrogen bonds, while CpGs are bound with three. Such binding characteristics are expected to provide stability to CpGs compared to ApTs. This may explain the greater frequency of methylation in CpGs rather than ApTs in the

Methylation usually occurs through the addition of a methyl group to CpG sequence or to the C base in these CpG islands. Although such a change normally appears as a mutation, it is understood that, unlike mutations, this change is a highly functional mechanism in terms of cellular development and quite common across living organisms from bacteria to highly complex multicellular species. In this way, the organism can adapt to environmental changes by changing the activation of the desired genes in response to external influences when necessary, thereby maintaining vitality and survival. During a methylation reaction, 5-methylcytosine is formed with the addition of a methyl group to the fifth carbon of the cytosine in CpG base pairs by the DNA methyltransferase enzyme (**Figure 1**). Potentially, any CpG base pair or island may undergo methylation. In addition, the fourth nitrogen of cytosine and sixth nitrogen of adenine, which are usually not found in multicellular organisms, may also be methylated in addition to the 5-methylcytosine formation

Genomic imprinting is another example of DNA methylation that is involved in single-allele gene expression. Approximately 80 loci are suppressed in this way. The tissue-specific and condition-specific expressions of these genes occur through the regulation of methylation [12]. At the end of 1970s, a decrease in methylcytosine numbers was observed in the genome of tumour cells [13]. This was referred to as hypomethylation of DNA and was demonstrated in benign and malignant tumours [14]. Hypomethylation of DNA may also activate oncogenes. Studies have shown hypomethylation in SI00A4, a metastasis-associated gene in colorectal cancers and the genes, cyclin-D2 and maspin, in gastric carcinomas [14, 15]. Hypomethylation may cause loss of imprinting (LOI), thereby promoting cell proliferation. One of the best examples of this process is the loss of imprinting in the IGF2/H19 region, which is seen in about 40% of colorectal

Modulation of chromosome organisation is one of the host defence mechanisms against bacterial attacks in eukaryotes. The host cell can often resist bacteria through these highly special and successful defence mechanisms. However, bacteria also have mechanisms that are developed against this system. Some bacteria may contain eukaryote-like proteins and eukaryotic histone translation proteins, which target the chromosomal machinery. In this way, they can

CpG dinucleotides to cytosine [9, 10].

organism.

4 Chromatin and Epigenetics

in bacteria [11].

cancers [1].

**2. Bacterial epigenetic mechanisms**

activate appropriate enzymes in the host [16].

In all eukaryotic cells, mitochondrion is the most important organelle for cellular energy and the only organelle containing genomic material apart from the nucleus. Owing to its unique and small genome, this organelle exerts certain proteins and RNAs needed for respiratory reactions and cell growth. Together with the nucleus, it is one of the two genetic systems found in the cell. Mitochondrial DNA (mtDNA) has a circular structure and is located inside mitochondrial matrix, bound to the internal membrane. The mtDNA consists of 16,569 base pairs in a loop form, containing a heavy chain (H) and a light chain. This chain structure contains 2 rRNA molecules, 22 tRNA molecules, and 13 genes necessary for oxidative phosphorylation and electron transport (**Figure 2**). A healthy mitochondrion exerts adequate functions by means of certain proteins that are present in the mechanism of oxidative phosphorylation. This genome is about 16.5 kb in humans, and 13 proteins and rRNAs are synthesised from the mitochondrial genome in mammals [19, 20]. Therefore, the slightest change in mitochondrial genome can potentially affect the life of the cell, and thus the organism [21].

As is the case with mutations, methylation is a mechanism that alters the way the genes work together with the diet, drugs and oxidative stress. Methylation profile of human mtDNA starts from the intrauterine period. With the aid of foetal thyroid hormones, mtDNA copy number and mtDNA methylation are regulated by a thyroid-dependent pathway [23]. In addition, mtDNA is also affected by airway pollutants. The elemental carbon present in benzene and exhaust gas in traffic may influence the number of mtDNA copies by means of ribosomal RNA methylation [24].

**Figure 2.** Gene structure of mitochondrial genome [22].

Despite the understanding of these methylation changes in mitochondrial genome, the function of methylated mtDNA has not been fully understood; however, Monique et al. have revealed a different situation. Contrary to what is expected with the methylation of CpGs and GpCs in mtDNA, they have demonstrated that methylation of CpG base pairs had no effect on expression while methylated GpCs were associated with decreased expression [25].

Furthermore, since the mitochondria in humans are entirely of maternal origin, life style of the mother may also have effects at mitochondrion level. Habitual behaviour of the mother, her diet and excessive consumption of fats and sugars trigger obesity, which may affect epigenetics, including that of mitochondria in subsequent generations. A study conducted in mice revealed increased methylation leading to alterations in gene expression and suppression, particularly in the respiratory tract of the offspring of mice that were fed high-fat diets [26]. Furthermore, because the structure of mitochondrion is highly similar to that of bacteria, some genetic factors and structures may also be the same.
