Transcription factor binding and nucleosome positioning are alternative pathways for transcription start site selection in eukaryotic promoters

The DNA sequence determinants which direct RNA Pol-II to the correct transcription start site (TSS) are only partly understood. Conserved DNA motifs (core promoter elements) or a conserved nucleosome architecture may play a role in TSS selection. A complicating factor is that promoters are quite variable in many respects. Some have very focused while others have highly dispersed initiation site patters. Promoters also differ by the presence or absence of CPEs. Here we show that promoters without CPEs have a strong sequence–intrinsic nucleosome– positioning signal in the +1 nucleosome region, in both vertebrates and flies. The strength of the signal is inversely proportional to the degree of TSS dispersion. Interestingly, the nucleosome–positioning signal is completely absent in CPE containing promoters. Together, these findings suggest that transcription factor binding to CPEs and DNA sequence– induced nucleosome positioning are two mutually exclusive pathways of Pol-II recruitment to TSSs in eukaryotic promoters.