DNA sequences at and between the GC and TATA boxes: potential DNA looping and spatial juxtapositioning of the protein factors.

Regulation of gene expression in eukaryotes involves a complex assembly of DNA recognition sequence elements and their respective protein factors. The upstream promoter/enhancer sequences are position and orientation independent. Despite their variable distances from the TATA box and transcription start site, interaction between the protein activators and TATA general transcription factors takes place, enabling induced levels of transcription initiation. Here the intervening sequences between the GC and TATA boxes are examined as functions of their lengths. Regardless of the substantial differences in the spacer sizes, similar mono and dinucleotide distributions are noted. Purine-purine base pair steps, except for AA, are more frequent at and near the GC box in the 5' ends of the loops than in their 3' ends. Pyrimidine-pyrimidine base pair steps, except for TT behave similarly. AT and TA (as well as AA and TT) are more frequent in the 3' ends of the loops near the TATA. Examination of these distributions, as well as of the sequences composing the GC and TATA boxes indicates that the DNA in the upstream part of the loop is more rigid, whereas the downstream regions are far more flexible. The flexibility of the general TATA region may afford correct spatial juxtapositioning of the proteins with respect to each other, enabling interactions between the activators and the general transcription factors.