Poster Sessions

BIOINFO-5

Damian Wojtowicz

D.M. Wojtowicz, F.E. Kouzine, A. Yamane, R.C. Casellas, D. Levens, T.M. Przytycka

Genome-wide Analysis of Alternative DNA Structures

DNA usually assumes double-stranded right-handed helix conformation known as B-DNA. However, DNA is a dynamic molecule that undergoes various deformations and adopts many alternative conformations such as single-stranded DNA, Z-DNA (left-handed), or quadruplex. Previous studies confirmed the existence of non-B-DNA conformation at some particular sites and their potential role in DNA transactions, e.g. the tight regulation of c-myc oncogene by FUSE element, but it is not known how general such a regulation mechanism might be. A number of computational approaches to uncover non-B-DNA regions have been developed but no genome scale confirmation of such predictions were possible. Thanks to the new experimental technique developed in David Levens group, we have an unprecedented opportunity to map non-B forms of DNA in vivo on the genomic scale. This allows, for the first, genome-wide analysis of occurrences of alternative structures and their position with respect to transcription start sites, etc. We find an enrichment of non-B-DNA conformations near transcription start sites indicative of their role in gene regulation. We compare the experimental data and the regions with a high propensity to form non-B-DNA structures to recognize the type of a particular structure. This offers not only strong evidence for the in vivo formation of the alternative structures like Z-DNA, quadruplexes and SIDD sites but also provides the first look at their genome-wide landscape.