Profiling the thermodynamic softness of adenoviral promoters

Abstract

We showed previously that anharmonic DNA dynamical features correlate with transcriptional activity in selected viral promoters, and hypothesized that areas of DNA softness may represent loci of functional significance. The nine known promoters from human adenovirus type 5 were analyzed for inherent DNA softness using the Peyrard-Bishop-Dauxois model and a statistical mechanics approach, using a transfer integral operator. We found a loosely defined pattern of softness peaks distributed both upstream and downstream of the transcriptional start sites, and that early transcriptional regions tended to be softer than late promoter regions. When reported transcription factor binding sites were superimposed on our calculated softness profiles, we observed a close correspondence in many cases, which suggests that DNA duplex breathing dynamics may play a role in protein recognition of specific nucleotide sequences and protein-DNA binding. These results suggest that genetic information is stored not only in explicit codon sequences, but also may be encoded into local dynamic and structural features, and that it may be possible to access this obscured information using DNA dynamics calculations.

FIGURE 1

Calculated propensity profiles showing soft areas for adenovirus 5 control sequences. A total of 200 bp were analyzed using a PBD-TIO method to calculate propensity of 10 bp openings starting at each basepair to analyze for DNA softness. The x axis reflects the global bp position based on the published genomic sequence.

FIGURE 2

Calculated propensity profiles showing soft areas for adenovirus 5 early promoters. A total of 200 bp of the promoter region around the transcriptional start site was analyzed using a PBD-TIO method to calculate propensity of 10 bp openings starting at each basepair to analyze for DNA softness. The x axis reflects the bp position relative to the TSS (+1), which is indicated by the right-facing arrow in the graph. Reported transcription factor binding sites or sites of protection from DNase I are indicated with bars above the softness profile and labeled with the name of the transcription factor. References for the binding sites are included in the Discussion.

FIGURE 3

Calculated propensity profiles showing soft areas for adenovirus 5 late promoters. A total of 200 bp of the promoter region around the transcriptional start site was analyzed using a PBD-TIO method to calculate propensity of 10 bp openings starting at each basepair to analyze for DNA softness. The x axis reflects the bp position relative to the TSS (+1), which is indicated by the right-facing arrow in the graph. Reported transcription factor binding sites or sites of protection from DNase I are indicated with bars above the softness profile and labeled with the name of the transcription factor. References for the binding sites are included in the Discussion.