Epilogue

Abstract

Advances made in the last decade have firmly established the critical role of the epigenome in orchestrating the complex and dynamic gene expression program of multicellular organisms such as humans. The epigenome is composed of two distinctly different layers of information, chromatin and DNA methylation. While chromatin is associated with the genome and serves to package its different regions in either tight or open structures, DNA methylation is part of the chemical covalent structure of the DNA. DNA methylation is there-fore believed to be a fixed component of the epigenome and to be a consistent and stable signal of gene inactivation. These two layers of information are tighdy correlated. DNA methylation is characteristic of inactive regions of the genome that are packaged in tight chromatin, whereas hypomethylated DNA is found in open and active chromatin structures. Recent advances in understanding the relation between chromatin and DNA methylation have provided some insights into the mechanisms that tie these processes to each other. It is clear that DNA methy-lation has to be understood within its chromatin context and aberrations in DNA methylation must be understood in relation to changes in chromatin structure and in the proteins that remodel chromatin. Cancer is a disease of foiled programming of gene expression and could be therefore considered an epigenomic disease. Aberrations in either one or both chromatin struc-ture and DNA methylation have been found by many studies to be a persistent hallmark of cancer. An understanding of DNA methylation changes and their diagnostic and therapeutic implications in cancer could only be achieved if they are analyzed in the context of the chromatin.