Inferring the in vivo looping properties of DNA
- Integrative Biological Modeling Laboratory, Computational Biology Program, Memorial Sloan–Kettering Cancer Center, 307 East 63rd Street, New York, NY 10021
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Edited by Martin Gellert, National Institutes of Health, Bethesda, MD, and approved October 5, 2005 (received for review July 7, 2005)
Abstract
The free energy of looping DNA by proteins and protein complexes determines to what extent distal DNA sites can affect each other. We inferred its in vivo value through a combined computational–experimental approach for different lengths of the loop and found that, in addition to the intrinsic periodicity of the DNA double helix, the free energy has an oscillatory component of about half the helical period. Moreover, the oscillations have such an amplitude that the effects of regulatory molecules become strongly dependent on their precise DNA positioning and yet easily tunable by their cooperative interactions. These unexpected results can confer to the physical properties of DNA a more prominent role at shaping the properties of gene regulation than previously thought.
Footnotes
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↵ † To whom correspondence should be addressed. E-mail: vilar{at}cbio.mskcc.org.
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↵ * On leave from: Departament de Fisica Fonamental, Universitat de Barcelona, Diagonal 647, 08028 Barcelona, Spain.
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Author contributions: L.S., J.M.R., and J.M.G.V. designed research, performed research, analyzed data, and wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
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Freely available online through the PNAS open access option.
- Copyright © 2005, The National Academy of Sciences
