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Sequence dependence of transcription factor-mediated DNA looping.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Department of Physics and Department of Bioengineering, California Institute of Technology.
2012 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no 16, 7728-7738 p.Article in journal (Refereed) Published
Abstract [en]

DNA is subject to large deformations in a wide range of biological processes. Two key examples illustrate how such deformations influence the readout of the genetic information: the sequestering of eukaryotic genes by nucleosomes and DNA looping in transcriptional regulation in both prokaryotes and eukaryotes. These kinds of regulatory problems are now becoming amenable to systematic quantitative dissection with a powerful dialogue between theory and experiment. Here, we use a single-molecule experiment in conjunction with a statistical mechanical model to test quantitative predictions for the behavior of DNA looping at short length scales and to determine how DNA sequence affects looping at these lengths. We calculate and measure how such looping depends upon four key biological parameters: the strength of the transcription factor binding sites, the concentration of the transcription factor, and the length and sequence of the DNA loop. Our studies lead to the surprising insight that sequences that are thought to be especially favorable for nucleosome formation because of high flexibility lead to no systematically detectable effect of sequence on looping, and begin to provide a picture of the distinctions between the short length scale mechanics of nucleosome formation and looping.

Place, publisher, year, edition, pages
2012. Vol. 40, no 16, 7728-7738 p.
Keyword [en]
Lac repressor, DNA looping, DNA mechanics tethered particle motion
National Category
Biophysics
Research subject
Biophysics; Physical Biology; Physics
Identifiers
URN: urn:nbn:se:su:diva-83233DOI: 10.1093/nar/gks473PubMedID: 22718983OAI: oai:DiVA.org:su-83233DiVA: diva2:574615
Available from: 2012-12-06 Created: 2012-12-06 Last updated: 2017-12-07Bibliographically approved

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