Profiling the thermodynamic softness of adenoviral promoters
Year: 2008
Authors: Choi C.H., Rapti Z., Gelev V., Hacker M.R., Alexandrov B., Park E.J., Park J.S., Horikoshi N., Smerzi A., Rasmussen K.O., Bishop A.R., Usheva A.
Autors Affiliation: Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA; Harvard Univ, Sch Med, Boston, MA USA; Univ Illinois, Dept Math, Urbana, IL 61801 USA; Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02215 USA; Los Alamos Natl Lab, Ctr Nonlinear Studies, Div Theoret, Los Alamos, NM 87545 USA; Washington Univ, Dept Radiat Oncol, Sch Med, St Louis, MO USA.
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.
Journal/Review: BIOPHYSICAL JOURNAL
Volume: 95 (2) Pages from: 597 to: 608
More Information: The authors acknowledge financial support from the National Institutes of Health-National Institute of General Medical Sciences (grant No. R01 GM073911 to A.U.). Research at Los Alamos is carried out under the auspices of the National Nuclear Security Administration of the U.S. Department of Energy at Los Alamos National Laboratory under Contract No. DE-AC52-06NA25396 to K.R.KeyWords: Major Late Promoter; 2 Transcription Factors; Polypeptide-ix Gene; Rna-polymerase-ii; Dna-binding; Start Sites; Stimulates Transcription; Activates Transcription; Factors Interact; Core PromoterDOI: 10.1529/biophysj.107.123471Citations: 21data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-10-20References taken from IsiWeb of Knowledge: (subscribers only)