Toward a Detailed Description of the Thermally Induced Dynamics of the Core Promoter
Alexandrov, Boian S.
Yoo, Sang Wook
Bishop, Alan R.
Rasmussen, Kim Ø.
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CitationAlexandrov, Boian S., Vladimir Gelev, Sang Wook Yoo, Alan R. Bishop, Kim Ø. Rasmussen, and Anny Usheva. 2009. Toward a detailed description of the thermally induced dynamics of the core promoter. PLoS Computational Biology 5(3): e1000313.
AbstractEstablishing the general and promoter-specific mechanistic features of gene transcription initiation requires improved understanding of the sequence-dependent structural/dynamic features of promoter DNA. Experimental data suggest that a spontaneous dsDNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we use Langevin molecular dynamic simulations based on the Peyrard-Bishop-Dauxois nonlinear model of DNA (PBD LMD) to analyze the strand separation (bubble) dynamics of 80-bp-long promoter DNA sequences. We derive three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable dsDNA openings do not necessarily coincide with the most probable openings and the highest average strand displacement, underscoring the advantages of proper molecular dynamic simulations. The dynamic profiles of the tested mammalian promoters differ significantly in overall profile and bubble probability, but the transcriptional start site is often distinguished by large (longer than 10 bp) and long-lived transient openings in the double helix. In support of these results are our experimental transcription data demonstrating that an artificial bubble-containing DNA template is transcribed bidirectionally by human RNA polymerase alone in the absence of any other transcription factors.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10178300
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