This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.107.111245v1 93/8/2726    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Polikanov, Y. S. Articles by Studitsky, V. M. Search for Related Content PubMed PubMed Citation Articles by Polikanov, Y. S. Articles by Studitsky, V. M.

Probability of the Site Juxtaposition Determines the Rate of Protein-Mediated DNA Looping

Yury S. Polikanov ^*, Vladimir A. Bondarenko ^*, Vladimir Tchernaenko , Yong I. Jiang ^*, Leonard C. Lutter , Alexander Vologodskii  and Vasily M. Studitsky ^*

^* Department of Pharmacology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854; Molecular Biology Research Program, Henry Ford Hospital, Detroit, Michigan 48202; and Department of Chemistry, New York University, New York, New York 10003

Correspondence: Address reprint requests to Alexander Vologodskii, Dept. of Chemistry, New York University, New York, NY 10003. E-mail: alex.vologodskii{at}nyu.edu.

Numerous biological processes are regulated by DNA elements that communicate with their targets over a distance via formation of protein-bridged DNA loops. One of the first questions arising in studies of DNA looping is whether the rate of loop formation is limited by diffusion of the DNA sites. We addressed this question by comparing the in vitro measured rates of transcription initiation in the NtrC-glnAp2 enhancer-dependent transcription initiation system with predictions of two different theoretical models. The promoter and enhancer were in a 7.6-kb plasmid and separated by 2.5 kb. The measurements were performed for different values of the plasmid superhelix density, from 0 to –0.07. Earlier theoretical analysis, based on the Monte Carlo simulation of DNA conformations, showed that if the rate of loop formation is determined by the equilibrium probability of juxtaposition of the DNA sites, the rate should be 100 times higher in supercoiled than in relaxed DNA. On the other hand, Brownian dynamics simulation showed that if the rate of loop formation is limited by the site diffusion, it should be nearly independent of DNA supercoiling. We found that efficiency of the transcription initiation increases by nearly two orders of magnitude as a result of the corresponding increase of the template supercoiling. This clearly shows that the rate of bridging in the enhancer-promoter system is not limited by diffusion of the DNA sites to one another. We argue that this conclusion derived for the specific system is likely to be valid for the great majority of biological processes involving protein-mediated DNA looping.

This article has been cited by other articles:

				L. E. Catto, S. R. W. Bellamy, S. E. Retter, and S. E. Halford Dynamics and consequences of DNA looping by the FokI restriction endonuclease Nucleic Acids Res., April 1, 2008; 36(6): 2073 - 2081. [Abstract] [Full Text] [PDF]