Sequence-specific thermal fluctuations identify start sites for DNA transcription

¹ Theoretical Division and Center for Nonlinear Studies Los Alamos National Laboratory - Los Alamos, NM 87545, USA
² Endocrinology, Beth Israel Deaconess Medical Center Department of Medicine, Harvard Medical School 99 Brooklin Ave., Boston, MA 02215, USA

Received: 12 May 2004
Accepted: 28 July 2004

Abstract

We report successful comparisons between model predictions for intrinsic thermal openings and experimental transcription data, showing that large and slow thermally induced openings (bubbles) of double-stranded DNA coincide with the location of start sites for transcription. Investigating viral and bacteriophage DNA gene promoter segments, we find that the largest opening occurs at the transcription start site in all cases studied. Other probable large openings predicted in our model appear to be related to other regulatory sites. The coherent dynamics is determined by a combination of sequence specificity (disorder), nonlinearity, and entropy, controlled by the long-range consequences of local base-pair stacking constraints.