Epigenetics of Chromatin Dynamics: DNA-methylation versus histone 3 modifications during tumor development and cancer progression

Abstract

Epigenetic mechanisms of gene expression are involved with DNA cytosine-5-carbon methylation (hereafter, DNA methylation) and modifications of histones with numbers of chemical groups (methyl, acetyl, phosphate and ubiquityl etc.) at multiple positions of histones at amino acids lysine, arginine and serine side chains. Among these modifications; DNA methylation puts an additional layer of gene silencing information and histone modifications dispatch either silencing or activating signal depending on chemical groups and position of the amino acid in the histone chains. For example, H3K4me3 is an active signal whereas H3K9me3 and H3K27me3 are repressive signals. Although gene specific mechanisms of activation and repression emerged in the past two decade yet there are many ambiguities with respect to bivalent signatures – i. e., what will happen if there are both the signatures? Such phenomenon with histone marks are partially solved comparing histonemodifications only; however, our laboratory is dealing with repressive signals (DNA methylation) versus activation (for examples, H3K4me3 and H3K9acS10p) signals. In this context we have deciphered CAV1, OCT4, CLU and several miRNA genes regulation in multiple cancers. We analyzed these genes expression and associated epigenetic marks in the respective promoter in cancer cell lines by DNA methylation specific PCR, bisulphite modification of DNA and ChIP analyses following PCR. It is noteworthy that promoter DNA methylation of miR-152 gene kept it inactive while there was significant enrichment of H3K4me3. On the other side for protein coding genes CAV1, OCT4 and CLU, histone modifications and not DNA methylation are epigenetic regulator(s) of their expression in cancer. Our works provides novel insights of gene regulation and enhance the amplitude of the cancer epigenome.