Epigenetic Modifications: Genetic Basis of Environmental Stress Response

Abstract

Genomic DNA is faithfully replicated and divided between two daughter cells in the course of each cell cycle. In order to maintain the inheritance of gene expression patterns, the cell must not only replicate the DNA, but also duplicate its chromatin structure (McNairn & Gilbert, 2003). Following replication, DNA is methylated and packaged into nucleosomes by the binding of histone octamers to form chromatin. DNA methyltransferases (DNMTs), the enzymes that transfer methyl (CH3) residue to CpG dinulcleotides, are coordinated with DNA replication to maintain the DNA methylation pattern (Fig. 1). DNMTs recognize methylated CpG dinucleotides on the parent strand and methylate correlating CpG dinucleotides on the daughter strand (Bestor et al., 1996). This heritability of the DNA methylation pattern, as well as histone modification patterns, is mediated by epigenetic machinery. Epigenetics was first used by Conrad Waddington in 1939 to describe “the causal interactions between genes and their products, which bring the phenotype into being” (Waddington, 1942). The current definition is “the study of heritable changes in gene expression that occur independent of changes in the primary DNA sequence” (Sharma et al., 2010). Waddington’s definition initially referred to the role of the epigenetics in embryonic development, in which cells develop distinct identities despite having the same genetic information; however, the definition of epigenetics has evolved over time as it is implicated in a wide variety of biological processes, including maintenance of the normal gene expression, carcinogenesis and genomic response to environmental stresses. In this chapter, we take a look at the courent understanding of epigenetic status in human cells, describe human diseases associated with congentital epigenetic errors, and also discuss how human diseases may be caused by acquired epigenetic errors as a result of environmental factors. We also discuss epigenetic therapies that take advantage of the fact that epigenetic changes are resversible.