The relationship between fine scale DNA structure, GC content, and functional elements in 1% of the human genome.

Abstract

GC content has been shown to be an important aspect of human genomic function. Extending beyond the scope of GC content alone, there is a class of regions in the genome that have especially high GC content and are enriched for the CG dinucleotide--called CpG islands. CpG islands have been linked to biologically functional genomic elements. DNA structure also contributes to biological function. Recent studies found that some DNA structural properties are correlated with CpG island functionality. Here, we use hydroxyl radical cleavage patterns as a measure of DNA structure, to explore the relationship between GC content and fine-scale DNA structure. We show that there is a positive correlation between GC content and the solvent-accessible structural properties of a DNA sequence, and that the strength of this correlation decreases as genomic resolution increases. We demonstrate that regions of the genome that have highly solvent-accessible DNA structure tend to overlap functional genomic elements. Our results suggest that fine-scale DNA structural properties that are encoded in the genome are important for biological function, and that the highly solvent-accessible nature of high GC content regions and some CpG islands may account for some of their functional properties.