Introduction
Normal cells continually undergo genetic changes that transform their genomes to adapt to environmental stresses. Epigenetics is a term used to refer to reversible, heritable changes in the expression of genes that occur without spontaneous mutations. These occurrences mostly involve posttranslational modifications of histones and the methylation of DNA, both having profound effect on the expression of genes.
Citing Kumar, Abbas, Aster, and Robbins, (2013), most normal, differentiated cells have a major portion of their genome not expressed (silent genes). DNA methylation and histone modifications are both responsible for the modifications that silence such genes. In contrast, a common characteristic of most cancers is the global DNA selective promoter localized hypermethylation and hypomethylation. These have been proven in the past years with the discovery that tumor suppressor genes (like Tp53 and DNA repair genes) are sometimes silenced by hypermethylation of upstream promoter sequences rather than by mutations. In mice, Genome wide hypomethylation has been proved to cause chromosomal instability and can induce tumors. Thus, epigenetic changes may influence carcinogenesis in many ways.
Epigenetics also involves the study of how the environment affects the expression of somatic genes. For example, studies indicate that both diabetes mellitus and hypertension have a genetic component and an environmental component that act synergistically to influence the phenotypic characteristics of the diseases. (Herceg and Ushijima, (2010)). So far, among all the epigenetics research conducted, cancer is the most extensively studied disease, and the evidence linking epigenetic processes with cancer can be concluded to becoming “extremely compelling,” says Peter Jones, director of the University of Southern California’s Norris Comprehensive Cancer Center. Below is a brief explanation of the multiple mechanisms of epigenetics.
DNA methylation
DNA methylation serves to inhibit gene expression in somatic cells. It is kind of a switch on and off mechanism for the genome. The process can be both active (leading to transcriptional and repression) and passive (in newly synthesized DNA strands). Methylation of DNA is a tightly regulated process in the genome. DNA methyltrtransferases (enzymes) establish and maintain DNA methylation. The 5-mc protein in DNA methylation has been implicated as a major epigenetic modification occurring in genetic expression and phenotypic modifications. According to Kumar, Abbas, Aster and Robbins, (2013), it is becoming more and more evident that hypomethylation of DNA can be caused deficiency of methyl (environmental factor) and has consequently been proposed as a molecular marker in cancer. The first ever DNA methylation to be confirmed in human cancer was in 1983. Various organizations have been established to focus on DNA methylation and demethyltion and create databases to assemble known DNA methylations- providing useful tools for research and investigations.
Chromatin remodeling