Skip Navigation


Nucleic Acids Research Advance Access originally published online on December 1, 2007
Nucleic Acids Research 2008 36(3):726-731; doi:10.1093/nar/gkm1034
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (236K) Freely available
Right arrow Screen PDF (216K) Freely available
Right arrowOA All Versions of this Article:
36/3/726    most recent
gkm1034v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Saiz, L.
Right arrow Articles by Vilar, J. M. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Saiz, L.
Right arrow Articles by Vilar, J. M. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2008, Vol. 36, No. 3 726-731
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Computational Biology

Ab initio thermodynamic modeling of distal multisite transcription regulation

Leonor Saiz and Jose M. G. Vilar*

Integrative Biological Modeling Laboratory, Computational Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

*To whom correspondence should be addressed. Tel: +1 646 888 2603; Fax: +1 646 422 0717; Email: vilar{at}cbio.mskcc.org

Received September 18, 2007. Revised October 29, 2007. Accepted October 29, 2007.

Transcription regulation typically involves the binding of proteins over long distances on multiple DNA sites that are brought close to each other by the formation of DNA loops. The inherent complexity of assembling regulatory complexes on looped DNA challenges the understanding of even the simplest genetic systems, including the prototypical lac operon. Here we implement a scalable approach based on thermodynamic molecular properties to model ab initio systems regulated through multiple DNA sites with looping. We show that this approach applied to the lac operon accurately predicts the system behavior for a wide range of cellular conditions, which include the transcription rate over five orders of magnitude as a function of the repressor concentration for wild type and all seven combinations of deletions of three operators, as well as the observed induction curves for cells with and without active catabolite activator protein. Our results provide new insights into the detailed functioning of the lac operon and reveal an efficient avenue to incorporate the required underlying molecular complexity into fully predictive models of gene regulation.

Present address: Leonor Saiz, Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.