Dynamical signature of the core promoter

ABSTRACT

Establishing 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 DNA strand separation at the transcriptional start site is likely to be a requirement for transcription initiation in several promoters. Here, we will describe our attempts to use simulations to analyze the strand separation (bubble) dynamics of 80-base-pair-long promoter DNA sequences. We argue that three dynamic criteria, bubble probability, bubble lifetime, and average strand separation, are needed to characterize bubble formation at the transcriptional start sites of eight mammalian gene promoters. We observe that the most stable DNA 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 base pair) and long-lived transient openings in the double helix. In strong support of our simulation based arguments 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.