**1. Introduction**

### **1.1 Epigenetics**

Epigenetics is the study of the variations of genetic expression that has been referred to the heritable changes in gene expression without changes in the DNA sequence and described the interactions between the genome and the environment that leads to the formation of the phenotype [1]. Epigenetic modifications such as DNA methylation and histone modifications are able to affect gene expression mostly by interfering with transcription factors with DNA or may lead to structural rearrangement of chromatin thus promoting the expression of particular genes. These epigenetic mechanisms are those that alter the chromatin structure including DNA methylation of cytosine residues in CpG dinucleotides and post-translational histone modifications. Epigenetic regulations occur not because of differences in DNA structure, but because of chromatin alternations that modulate DNA transcription such as DNA methylation, that can mediate gene and environment interactions at the level of the genome. The mechanisms of epigenetics are thus the link between genome and phenotype [1, 2]. Epigenetic mechanisms play an important role in regulating gene expression. The main mechanisms are methylation of DNA and modifications of histones by methylation, acetylation, phosphorylation. Modifications in DNA methylation are performed by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, and by enzymes, such as histone acetyltransferases (HATs), histonedeacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs) that regulate covalent histone modifications. In many diseases, such as cancer, the epigenetic regulatory system is disturbed [2]. MicroRNAs (miRNAs) are another epigenetic regulatory system that influences the regulation of gene expression, which are small RNA molecules, ∼22 long nucleotides, that can bind to their target miRNAs and downregulate their stabilities and/or translation [3]. Recent investigations have shown the association of altered expression of noncoding RNAs in general and miRNAs in particular with epigenetic modifications [2–4], suggesting that epigenetic alterations can contribute to the carcinogenesis [3] and are considered a hallmark of cancer [4].
