DNA-STRUCTURE IN HUMAN RNA-POLYMERASE-II PROMOTERS

The fact that DNA three-dimensional structure is important for transcr iptional regulation begs the question of whether eukaryotic promoters contain general structural features independently of what genes they c ontrol. We present an analysis of a large set of human RNA polymerase IT promoters with a very low level of sequence similarity. The sequenc es, which include both TATA-containing and TATA-less promoters, are al igned by hidden Markov models. Using three different models of sequenc e-derived DNA bendability, the aligned promoters display a common stru ctural profile with bendability being low in a region upstream of the transcriptional start point and significantly higher downstream. Inves tigation of the sequence composition in the two regions shows that the bendability profile originates from the sequential structure of the D NA, rather than the general nucleotide composition. Several trinucleot ides known to have high propensity for major groove compression are fo und much more frequently in the regions downstream of the transcriptio nal start point, while the upstream regions contain more low-bendabili ty triplets. Within the region downstream of the start point, we obser ve a periodic pattern in sequence and bendability, which is in phase w ith the DNA helical pitch. The periodic bendability profile shows bend ing peaks roughy at every 10 bp with stronger bending at 20 bp interva ls. These observations suggest that DNA in the region downstream of th e transcriptional start point is able to wrap around protein in a mann er reminiscent of DNA in a nucleosome. This notion is further supporte d by the finding that the periodic bendability is caused mainly by the complementary triplet pairs CAG/CTG and GGC/GCC, which previously hav e been found to correlate with nucleosome positioning. We present mode ls where the high-bendability regions position nucleosomes at downstre am end of the transcriptional start point, and consider the possibilit y of interaction between histone-like TAFs and this area. We also prop ose the use of this structural signature in computational promoter-fin ding algorithms. (C) 1998 Academic Press.