Synergy of human Pol II core promoter elements revealed by statistical sequence analysis

Motivation: The subject of our paper is bioinformatics analysis of the distinguishing features of human promoter DNA sequences, in particular of synergetic combinations of core promoter elements therein. We suppose that specific scenarios of transcription initiation are essentially related to various particular implementations of the interaction of basal transcription machinery with promoter DNA, depending on the presence and mutual positioning of core promoter elements. Results: In addition to the combinations of core promoter elements previously experimentally confirmed [TATA box and Initiator (Inr), Downstream Promoter Element (DPE) and Inr, and TFIIB recognition element (BRE) and TATA box] we propose other alternate synergetic combinations: BRE and Inr, BRE and DPE, and TATA and DPE with respective models. The suggestion is based on a high statistical significance of the alternate combinations in promoters, comparable with the significance of the known combinations. We also present arguments that the BRE element is statistically more important than previously thought, and suggest possible mechanisms of action of the core elements in the promoters with multiple transcription start sites.