Curvature and sequence analysis of eukaryotic promoters.

We have calculated the curvature of 504 eukaryotic promoters predicted by the bent A-tract model of Bolshoy et al. (Proc. Natl. Acad. Sci. USA, 88(6), pp. 2312-16) and the bent non-A-tract models of Calladine et al. (J. Mol. Biol., 201, pp. 127-37) and Satchwell et al. (J. Mol. Biol., 191, pp. 659-75) and found in each case a correlation between TBP binding sites and DNA curvature. Characterizing the TBP binding sites revealed that in addition to the classical TATA box (TATAAA) five more elements occur significantly often in the promoters, nearly all of them being one point mutations of the classical TATA box element. Separate curvature calculations for promoters with canonical and non-canonical TATA boxes have shown that in both cases the strong curvature of the helix axes in the domain of the binding sites is maintained (classical TBP binding sites: + 64-135%, non-classical TBP binding sites: + 27-49%). These results support the proposition that beside DNA flexibility and DNA-protein interactions intrinsic curvature of DNA is one further important criterion for the recognition of different DNA elements by TBP.