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DNA Structure and Sequence Periodicity in Human Promoters

Anders Gorm Pedersen, Pierre Baldi, Yves Chauvin and Soren Brunak

DNA structure has been found to influence initiation of transcription in many ways. Thus, packaging of DNA into chromatin inhibits transcription, and in accordance with this a number of transcription factors and transcriptional co-activators have recently been shown to be histone acetylases. Local bending and looping of DNA at promoters and enhancers is also believed to be important for the initiation process. In all cases, DNA structure is likely to be the result of the combined effects of proteins that actively distort the DNA-structure locally, and the intrinsic bendability and structure of the DNA. The fact that intrinsic DNA structure seems to be important for promoter function led us to investigate whether eukaryotic promoters might contain general structural features, independently of what genes they control. In order to investigate this problem we used hidden Markov models (HMMs) to align a set of human promoters with very low sequence similarity, and subsequently analyzed the promoter DNA structure based on this alignment. Interestingly, we do find a common structural profile with DNA bendability being low just upstream of the transcriptional start point, and significantly higher downstream. Within the downstream region, bendability was found to be periodic and in phase with the DNA helical pitch, suggesting that the DNA in this region is able to wrap around protein. We discuss the possible biological significance of this finding with regard to histone-like TAFs (TATA binding protein associated factors), and with regard to the possible effects this DNA structure may have on strand separation at initiation of transcription. We also propose the use of this structural signature in promoter finding.

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