Modeling Transcription Initiation By Bacterial RNA Polymerase

Abstract

Bacterial RNA polymerase (RNAP) is the central enzyme of gene expression, and initiation of transcription by RNAP is both the first step and a major point in regulation of gene expression. As a first step of transcription initiation, RNAP binds to double stranded DNA and opens the two strands of DNA, which is referred to as the open complex formation. A question of how the open complex is formed still remains open, despite significant experimental efforts over the last two decades [1].We develop the first quantitative model of the open complex formation by bacterial RNAP, which provides a theoretical framework needed to analyze the assembled experimental data. The model is based on statistical physics and establishes an explicit relationship between the rate of transcription initiation and biophysical properties of promoter sequence and promoter-RNAP interactions [2]. We compare our model with both biochemical measurements and genomics data and report a very good agreement with the experiments, with no free parameters used in model testing. Qualitatively, our model strongly supports a hypothesis by which the open complex formation is a two step process, where the transcription bubble is first formed in the -10 region and consequently extended to the transcription start site. Quantitatively, our results allow efficient estimation of promoter kinetic parameters for any given DNA sequence, as well as ‘engineering’ of promoter sequences with the desired kinetic properties. Finally, we discuss how our biophysical model can be used to investigate kinetic properties of promoter sequences on a genome wide scale [3].[1] Young, B.A., T.M. Gruber, and C.A. Gross. Science 303:1382-1384 (2004).[2] M. Djordjevic and R. Bundschuh. Biophysical Journal 94: 4233-4248 (2008).[3] M. Djordjevic. Quantitative analysis of promoter kinetic properties on a genome-wide scale (to be submitted, 2008).