**2. Role of epigenetic enzymes in human diseases**

Epigenetics is the study of mechanisms that results in heritable changes in gene expression without the alteration of the genetic code [29]. The deregulation of epigenetic mechanisms, such as DNA methylation and histone modifications, have been reported to facilitate differential expression of genes, many of which underlie the etiology and/or the progression of human diseases [30].

These epigenetic mechanisms are mediated by their respective epigenetic enzymes. For instance, DNA methyltransferases (DNMTs) coordinate the methylation of DNA by catalyzing the transfer of a methyl group to cytosine (C) from the donor molecule S-adenosylmethionine (SAM) [31]. The methylated DNA is read by methyl-Cp-guanine (G) binding domains (MBD) protein. DNA methylation can be reversed by a group of human demethylase enzymes termed ten-eleven translocation proteins (TET 1/2/3) [31]. DNA methylation is responsible for gene silencing and often occurs in regions rich in C and G nucleotides, also known as CpG islands. The catalysis of DNA methylation is primarily conducted by the following family of DNMTs: DNMT1, DNMT3A, and DNMT3B [32]. These enzymes help maintain the integrity of the human genome, regulate transcriptional processes, and aid cellular development and differentiation [33]. Thus, dysregulation of DNA methyltransferase and demethylases are implicated in several human diseases.

Similarly, the covalent modification of histones is another facet of epigenetics that plays a pivotal role in human diseases. The core histone proteins, H2A, H2B, H3, and H4, form an octameric structure that wraps about 146 base pairs of DNA to form a nucleosome, and the linker histone, H1, connects the repeating nucleosomes that make up the chromatin. Histones' terminal regions project out of the chromatin in a tail-like structure, and these tails are subjected to post-translational modification (PTM) by different histone-modifying enzymes [28, 31]. Some of the most common classes of histone-modifying enzymes include histone acetyltransferases (HATs), histone deacetylases (HDACs), histone methyltransferases (HMTs), and histone demethylases (HDMs) [34]. HATs and HDACs are writers and erasers of acetylation, respectively, on lysine (K) residues of histones and non-histone proteins. The acetylation of histones results in a relaxed chromatin that promotes gene transcription [35]. HATs are classified into Type A: p300/CBP, general control

#### *Repurposing Market Drugs to Target Epigenetic Enzymes in Human Diseases DOI: http://dx.doi.org/10.5772/intechopen.101397*

non-depressible 5 (GCN5)-related N-acetyltransferase (GNAT), Moz, Ybf2/Sas3, Sas2, Tip60 (MYST), nuclear receptor coactivator- (NCOA-) related HAT, and transcription factor-related HAT; and Type B: HAT1, HAT2, HatB3.1, Rtt109, and HAT4 [36]. While HDACs comprise 18 enzymes: HDAC1-11 and sirtuins (SIRT)1-7 [37]. The BRD and extra terminal domain (BET) proteins are responsible for recognizing K residues that are acetylated [37]. On the other hand, methylation of histones, which occurs on either K or arginine (R) residues of histones, can lead to gene transcription repression or activation. The addition of methyl group(s) to histones is mediated by HMTs while its removal is mediated by HDMs [34]. HMTs are further subdivided into lysine methyltransferases (KMTs) and arginine methyltransferases (PRMTs) [38]. Similarly, HDMs are classified into lysine demethylase 1 (LSD1 or KDM1) and Jumonji C (JmjC) domain-containing histone demethylases [39]. Together, these classes of histone-modifying enzymes regulate the expression of genes vital to many human biological processes.
