The Epigenome

Abstract

The identity of each cell in a multi-cellular organism is determined by the unique gene expression pattern of that cell type. This identity must be remembered and passed on to daughter cells by epigenetic mechanisms, which are heritable changes without involving changes in DNA sequence. The epigenome is the combination of all chromatin modifications in any given cell type, i.e. DNA methylation and post-translational histone modifications. Accordingly, complex organisms, such as humans do not have a single epigenome, but instead have multiple epigenomes depending on the tissue type and developmental stage.

DNA methylation is the addition of a methyl group to the cytosine in a CpG dinucleotide. CpG islands are associated with most human core promoter regions and de novo methylation of such regions leads to silencing of the respective genes. Both DNA methylation and histone modification are involved in establishing patterns of gene repression during development. Histone methylation causes local formation of heterochromatin, which is readily reversible, whereas DNA methylation leads to stable long-term repression. DNA methylation and histone modification pathways can be dependent on each other, which is mediated by interactions between HMTs and DNA methyltransferases (DNMTs).

Aberrant DNA methylation is a well-established marker of cancer leading to inactivation of tumor suppressor genes, disturbance in genomic imprinting and genomic instabilities through reduced heterochromatin formation on repetitive sequences.

In this chapter, we present the impact of DNA methylation in the epigenomic processes during embryogenesis and inheritance. We will discuss the role of DNA methylation in the formation of heterochromatin and subsequent gene silencing. We will learn that the processes of DNA methylation and histone modification work closely together, but that their misregulation can be the cause of a number of diseases, such as cancer.