Epigenetic mechanisms and genome stability

Abstract

Epigenetic marks are well recognized as heritable chemical modifications of DNA and chromatin that induce chromatin structural changes thereby affecting gene activity. A lesser-known phenomenon is the pervasive effects these marks have on genomic integrity. Remarkably, epigenetic marks and the enzymes that establish them are involved in multiple aspects of maintaining genetic content. These aspects include preserving nucleotide sequences such as repetitive elements, preventing DNA damage, functioning in DNA repair mechanisms and chromatin restoration, and defining chromosomal organization through effects on structural elements such as the centromere. This review discusses these functional aspects of epigenetic marks and their effects on human health and disease.

Fig. 1

Chromosomal definition by histone modifications. Many molecules, including histone-modifying enzymes, histone variants, and DNA methyltransferases, some of which are depicted here on the left, establish the epigenetic marks and chromatin structure required for chromosomal organization and function. On the right, distinct combinations of histone modifications define chromatin regions including the centromere and pericentromere that organize and stabilize the chromosome as a whole and maintain genetic stability throughout repeated cell divisions