Nucleic Acids Research Advance Access originally published online on May 25, 2007
Nucleic Acids Research 2007 35(11):e80; doi:10.1093/nar/gkm268
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Nucleic Acids Research, 2007, Vol. 35, No. 11 e80
© 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.
Methods Online |
General transfer matrix formalism to calculate DNA–protein–drug binding in gene regulation: application to OR operator of phage 
Institute of Bioorganic Chemistry, Belarus National Academy of Sciences, Street Kuprevich 5/2, 220141, Minsk, Belarus
*To whom correspondence should be addressed. Tel: +375 17 267 82 63; Fax: +375 17 267 86 47; Email: teif{at}iboch.bas-net.by
Received February 2, 2007. Revised April 9, 2007. Accepted April 9, 2007.
The transfer matrix methodology is proposed as a systematic tool for the statistical–mechanical description of DNA–protein–drug binding involved in gene regulation. We show that a genetic system of several cis-regulatory modules is calculable using this method, considering explicitly the site-overlapping, competitive, cooperative binding of regulatory proteins, their multilayer assembly and DNA looping. In the methodological section, the matrix models are solved for the basic types of short- and long-range interactions between DNA-bound proteins, drugs and nucleosomes. We apply the matrix method to gene regulation at the OR operator of phage 
. The transfer matrix formalism allowed the description of the -switch at a single-nucleotide resolution, taking into account the effects of a range of inter-protein distances. Our calculations confirm previously established roles of the contact CI–Cro–RNAP interactions. Concerning long-range interactions, we show that while the DNA loop between the OR and OL operators is important at the lysogenic CI concentrations, the interference between the adjacent promoters PR and PRM becomes more important at small CI concentrations. A large change in the expression pattern may arise in this regime due to anticooperative interactions between DNA-bound RNA polymerases. The applicability of the matrix method to more complex systems is discussed.