Bidding the CpG island goodbye

John M Greally

doi:10.7554/elife.00593

Abstract

Experiments on seven vertebrates suggest that identifying the locations of islands of non-methylated DNA provides more insights into evolutionarily-conserved epigenetic regulatory elements than studies of CpG islands.

Highlights

Image Percentage of non-methylated islands of DNA conserved among seven vertebrates. It is almost 26 years since the CpG island— a stretch of DNA with a larger than expected proportion of cytosine followed by guanine bases—was first defined, based on an analysis of the relative proportions of the four bases in the limited amount of human sequence inform ation available (Gardiner-Garden and Frommer, 1987). These islands of CpG dinucleo tides were presumed to be the location of cisregulatory elements and, in particular, to be the location of gene promoters
The question that emerges is whether the CpG island annotation merely acts as a surrogate for an absence of DNA methylation, which is much more relevant when we are searching for cis-regulators in the genome
They report that when they looked for loci that escape DNA methylation in a set of non-human genomes, they found the CpG island annotation to be very poorly associated with these unmethylated loci (Long et al, 2013)

Summary

Introduction

During the past quarter century, we have sequenced numerous whole genomes from a wide range of species, and have witnessed the devel opment of powerful techniques for identifying cis-regulators throughout these whole genomes, yet we still persist with the concept of the CpG island when we annotate those parts of the genome that do not code for proteins. They report that when they looked for loci that escape DNA methylation in a set of non-human genomes, they found the CpG island annotation to be very poorly associated with these unmethylated loci (Long et al, 2013).

Results

Conclusion