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 in | Nucleic acids research Vol. 32; no. 4; pp. 1584 - 1590 |
|---|---|
| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Oxford University Press
2004
Oxford Publishing Limited (England) |
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| Abstract | 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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| AbstractList | 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. 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.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. |
| Author | Hiromura, Makoto Rasmussen, Kim Ø. Choi, Chu H. Kalosakas, George Bishop, Alan R. Usheva, Anny |
| AuthorAffiliation | 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 |
| AuthorAffiliation_xml | – name: 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 |
| Author_xml | – sequence: 1 givenname: Chu H. surname: Choi fullname: Choi, Chu H. – sequence: 2 givenname: George surname: Kalosakas fullname: Kalosakas, George organization: Center for Nonlinear Studies and Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA – sequence: 3 givenname: Kim Ø. surname: Rasmussen fullname: Rasmussen, Kim Ø. organization: Center for Nonlinear Studies and Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA – sequence: 4 givenname: Makoto surname: Hiromura fullname: Hiromura, Makoto – sequence: 5 givenname: Alan R. surname: Bishop fullname: Bishop, Alan R. organization: Center for Nonlinear Studies and Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA – sequence: 6 givenname: Anny surname: Usheva fullname: Usheva, Anny organization: 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 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15004245$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright Oxford University Press(England) Feb 15, 2004 Copyright © 2004 Oxford University Press 2004 |
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| Notes | 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 ark:/67375/HXZ-ZVGPBSP6-4 local:gkh335 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 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 |
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| Snippet | 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... 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... |
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| SubjectTerms | 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 |
| Title | DNA dynamically directs its own transcription initiation |
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