Published online 5 March 2004
Nucleic Acids Research, 2004, Vol. 32, No. 4 1584-1590
© 2004 Oxford University Press
DNA dynamically directs its own transcription initiation
Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Medicine, 99 Brookline Avenue, Boston, MA 02215, USA and 1 Center for Nonlinear Studies and Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
*To whom correspondence should be addressed. Tel: +1 617 632 0522; Fax: +1 617 632 2927; Email: ausheva{at}bidmc.harvard.edu
Present address:
Makoto Hiromura, Division of Cancer Biology and Institute for Genetic Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo 060-0815, Japan
It has long been known that double-stranded DNA is subject to temporary, localized openings of its two strands. Particular regions along a DNA polymer are destabilized structurally by available thermal energy in the system. The localized sequence of DNA determines the physical properties of a stretch of DNA, and that in turn determines the opening profile of that DNA fragment. We show that the Peyrard–Bishop nonlinear dynamical model of DNA, which has been used to simulate denaturation of short DNA fragments, gives an accurate representation of the instability profile of a defined sequence of DNA, as verified using S1 nuclease cleavage assays. By comparing results for a non-promoter DNA fragment, the adenovirus major late promoter, the adeno-associated viral P5 promoter and a known P5 mutant promoter that is inactive for transcription, we show that the predicted openings correlate almost exactly with the promoter transcriptional start sites and major regulatory sites. Physicists have speculated that localized melting of DNA might play a role in gene transcription and other processes. Our data link sequence-dependent opening behavior in DNA to transcriptional activity for the first time.
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