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Insights into transcriptional regulation and sigma competition from an equilibrium model of RNA polymerase binding to DNA.

ABSTRACT: To explore scenarios that permit transcription regulation by activator recruitment of RNA polymerase and sigma competition in vivo, we used an equilibrium model of RNA polymerase binding to DNA constrained by the values of total RNA polymerase (E) and sigma(70) per cell measured in this work. Our numbers of E and sigma(70) per cell, which are consistent with most of the primary data in the literature, suggest that in vivo (i) only a minor fraction of RNA polymerase (<20%) is involved in elongation and (ii) sigma(70) is in excess of total E. Modeling the partitioning of RNA polymerase between promoters, nonspecific DNA binding sites, and the cytoplasm suggested that even weak promoters will be saturated with Esigma(70) in vivo unless nonspecific DNA binding by Esigma(70) is rather significant. In addition, the model predicted that sigmas compete for binding to E only when their total number exceeds the total amount of RNA polymerase (excluding that involved in elongation) and that weak promoters will be preferentially subjected to sigma competition.

SUBMITTER: Grigorova IL

PROVIDER: S-EPMC1459355 | biostudies-literature | 2006 Apr

REPOSITORIES: biostudies-literature

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Insights into transcriptional regulation and sigma competition from an equilibrium model of RNA polymerase binding to DNA.

Grigorova Irina L IL Phleger Naum J NJ Mutalik Vivek K VK Gross Carol A CA

Proceedings of the National Academy of Sciences of the United States of America 20060327 14

To explore scenarios that permit transcription regulation by activator recruitment of RNA polymerase and sigma competition in vivo, we used an equilibrium model of RNA polymerase binding to DNA constrained by the values of total RNA polymerase (E) and sigma(70) per cell measured in this work. Our numbers of E and sigma(70) per cell, which are consistent with most of the primary data in the literature, suggest that in vivo (i) only a minor fraction of RNA polymerase (<20%) is involved in elongati ...[more]

PMID: 16567622

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Project description:BackgroundModeling of a complex biological process can explain the results of experimental studies and help predict its characteristics. Among such processes is transcription in the presence of competing RNA polymerases. This process involves RNA polymerases collision followed by transcription termination.ResultsA mathematical and computer simulation model is developed to describe the competition of RNA polymerases during genes transcription on complementary DNA strands. E.g., in the barley Hordeum vulgare the polymerase competition occurs in the locus containing plastome genes psbA, rpl23, rpl2 and four bacterial type promoters. In heat shock experiments on isolated chloroplasts, a twofold decrease of psbA transcripts and even larger increase of rpl23-rpl2 transcripts were observed, which is well reproduced in the model. The model predictions are in good agreement with virtually all relevant experimental data (knockout, heat shock, chromatogram data, etc.). The model allows to hypothesize a mechanism of cell response to knockout and heat shock, as well as a mechanism of gene expression regulation in presence of RNA polymerase competition. The model is implemented for multiprocessor platforms with MPI and supported on Linux and MS Windows. The source code written in C++ is available under the GNU General Public License from the laboratory website. A user-friendly GUI version is also provided at http://lab6.iitp.ru/en/rivals.ConclusionsThe developed model is in good agreement with virtually all relevant experimental data. The model can be applied to estimate intensities of binding of the holoenzyme and phage type RNA polymerase to their promoters using data on gene transcription levels, as well as to predict characteristics of RNA polymerases and the transcription process that are difficult to measure directly, e.g., the intensity (frequency) of holoenzyme binding to the promoter in correlation to its nucleotide composition and the type of σ-subunit, the amount of transcription initiation aborts, etc. The model can be used to make functional predictions, e.g., heat shock response in isolated chloroplasts and changes of gene transcription levels under knockout of different σ-subunits or RNA polymerases or due to gene expression regulation.

Dataset Information

Insights into transcriptional regulation and sigma competition from an equilibrium model of RNA polymerase binding to DNA.

Publications

Insights into transcriptional regulation and sigma competition from an equilibrium model of RNA polymerase binding to DNA.

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