DNA dynamically directs its own transcription initiation

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 stretc...

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Published inNucleic acids research Vol. 32; no. 4; pp. 1584 - 1590
Main Authors Choi, Chu H., Kalosakas, George, Rasmussen, Kim Ø., Hiromura, Makoto, Bishop, Alan R., Usheva, Anny
Format Journal Article
LanguageEnglish
Published England Oxford University Press 2004
Oxford Publishing Limited (England)
Subjects
Adeno-associated virus
Adenoviridae - genetics
Adenovirus
Base Sequence
Computer Simulation
Deoxyribonucleic acid
Dependovirus - genetics
DNA
DNA - chemistry
DNA, Single-Stranded - chemistry
Molecular Sequence Data
Nucleic Acid Denaturation
Physical properties
Polymers
Promoter Regions, Genetic
Thermal energy
Transcription Factor TFIIB - genetics
Transcription Initiation Site
Transcription, Genetic
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Summary: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.
Bibliography:istex:D1E0B18E49F4D5EB08BBCBEEDEA9A64266567CFF
To whom correspondence should be addressed. Tel: +1 617 632 0522; Fax: +1 617 632 2927; Email: ausheva@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
Received January 16, 2004; Revised and Accepted February 19, 2004
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Present address: Makoto Hiromura, Division of Cancer Biology and Institute for Genetic Medicine, Hokkaido University, N15, W7, Kita-ku, Sapporo 060-0815, Japan
To whom correspondence should be addressed. Tel: +1 617 632 0522; Fax: +1 617 632 2927; Email: ausheva@bidmc.harvard.edu
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkh335