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7413075 
Journal Article 
Overview of Epigenetic Signatures and Their Regulation by Epigenetic Modification Enzymes 
Ganai, SA; , 
2020 
Springer Singapore 
Singapore 
Histone Deacetylase Inhibitors in Combinatorial Anticancer Therapy 
1-33 
It is well endorsed in higher organisms that development and differentiation are strongly reliant on multiplex interactions between the genome and the surroundings (environment) (Aguilera et al. 2010). At the beginning the term epigenetics was used to refer these interactions. The word epigenetics was coined by Conrad Hall Waddington, a polymath scientist in 1942 (Waddington 1942). According to his opinion preformation and epigenesis are not independent but rather interdependent (Handy et al. 2011; Waddington 1942, 1968, 2012). All biologists are familiar that development begins from fertilized egg (zygote) containing certain “preformed” characters. These characters must interconnect with each other in processes of “epigenesis” prior to adulthood. Study restricted to these “preformed” characters, currently, is termed as genetics. The word “epigenetics” has been proposed for studying those processes composing epigenesis. From this discussion, it becomes crystal clear that the term “epigenetics” is nothing but reminiscent of “epigenesis” and has been derived from union of two terms “epigenesis” and “genetics” (Waddington 1956). According to Waddingtonian equation, epigenetics = epigenesis + genetics (Van Speybroeck 2002). Waddington’s meaning for development was the same what we call today differential gene expression and regulation. He introduced a metaphor for how gene regulation modifies development and that was “epigenetic landscape”. Actually he introduced this idea to explain the procedure of “decision making” in the course of development (Baedke 2013; Burbano 2006; Tronick and Hunter 2016; Waddington 1940). Almost 2 years after “epigenetic landscape” metaphor (1940), Waddington presented the term epigenetics (1942) as a refined version of this landscape (Tronick and Hunter 2016; Waddington 1942). About 15 years later in David Nanney’s article, the term epigenetic systems was used. According to him expression of genetically decided potentialities are controlled by epigenetic systems (Nanney 1958). Hall has defined epigenetics/epigenetic control as the sum total of genetic and non-genetic factors that act upon cells resulting in choosy regulation of gene expression generating elevated phenotypic complexity in the course of development (Burbano 2006; Wagner 1993). Robust technological refinement and in-depth studies on molecular biology gave timely amendments to the epigenetics. For instance the term heritable added to the usual Waddingtonian definition was a remarkable improvement (Holliday 2006; Holliday and Pugh 1975). Some use the term epigenetics for heritable alterations that are not due to change in nucleotide sequence of DNA (Wu and Morris 2001). Literally speaking, the term epigenetics means above or on top of genetics and thus designates external modifications (DNA methylation and histone post-translational modifications) turning genes on or off (Burbano 2006; Jablonka and Lamb 2002). Thus it is quite understandable that epigenetic modifications do not change actual DNA sequence but affect the reading of genes by cells. In other words, epigenetics may be defined as a regulatory system controlling gene expression without affecting their original makeup. Among the advanced definitions of epigenetics, one thing that usual DNA sequence is not altered stands firmly (Felsenfeld 2014; Ganai 2019; Goldberg et al. 2007; Tronick and Hunter 2016).