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The term "epigenetics" was first proposed by Conrad H. Waddington in 1942.1) Epigenetics is the study of acquired chemical modifications of DNA and nuclear histone proteins that do not alter the DNA sequence but regulate gene expression and other processes that occur during development, cell differentiation, and carcinogenesis.2) Among others, DNA methylation and histone modification are two well-researched physiological mechanisms of epigenetic change.3,4)
Mechanism of DNA methylation
Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosine. In mammals, methylating the cytosine within a gene can change its expression, a mechanism that is part of a larger field of science studying gene regulation called epigenetics. The enzymes that add methyl groups are called DNA methyltransferases and those that remove methyl groups are called DNA demethylases. Three types of each group have been identified in mammals.
Mechanism of Histone deacetylase (HDAC)
Genomic DNA is packaged in the nucleus as nucleosomes, each individual nucleosome consisting of a segment of DNA is wrapped around proteins called histones. Histone deacetylase (HDAC) is an important enzyme regulating gene expression by changing nucleosome structure. Numerous histone acetylases and deacetylases have been identified to date. HDAC is also thought to have a regulatory role in the cell cycle and cell differentiation, and the failure of this regulation has been associated with carcinogenesis. In a mouse model, SAHA [H1388] inhibited HDAC activity by inducing the differentiation and/or apoptosis of transformed cells in vitro, thereby inhibiting tumor growth.