How to build your own island

Abstract

Inserting artificially-generated 'DNA islands' into a genome has shed new light on why some DNA sequences are methylated and others are not.

Keywords: CpG islands; DNA methylation; bivalent chromatin; chromosomes; epigenetics; evolutionary biology; genes; genomics; high throughput genome editing; histone modifications; human; mouse.

Figure 1.. An artificial CpG island reveals its secrets.

(A) Wachter et al. inserted stretches of DNA that were G + C rich, and also had a high frequency of CpG sites, into an area of the genome that is devoid of genes (‘gene-poor region’). Histones associated with the DNA were assayed for histone marks: the number 2 indicates histones associated with the artificial CpG island; 1 and 3 indicate histones not associated with the island. (B) The CpG sites in these artificial islands remained unmethylated and recruited both activating and inactivating histone marks (labelled H3K4me3 and H3K27me3 respectively). The rows of open or filled circles represent unmethylated or methylated CpG sites; and the graph represents the frequency of each histone mark in different regions, in and around the artificial island. (C) Removal of CpG sites from the artificial island prevented the accumulation of both types of histone mark. (D) Decreasing the G + C content caused CpG sites to be over-methylated, which blocked histone modification. However, this could be overcome, at least in part, by either preventing CpG site methylation to begin with, or (as revealed by Krebs et al.) by adding a strong binding site for a transcription factor into the island which could drive its demethylation (arrow).