Periodical distribution of transcription factor sites in promoter regions and connection with chromatin structure

Nucleosomes regulate transcriptional initiation when positioned in the promoter area. This may require the transcription factor (TF) sites to be correlated with the nucleosome positions and phased on the nucleosome surface. If this is the case, one would expect a periodical distribution of TF sites in the vicinity of promoters, with the nucleosomal period of 10.1-10.5 bp. We examined the distributions of putative binding sites of 323 different TFs along 1, 057 sequences of the Eukaryotic Promoter Database (release 50) [Cavin Perier, R., Junier, T. & Bucher, P. (1998) Nucleic Acids Res. 26, 353-357] and of 218 TFs on 673 sequences of the Lead Exon Database of human promoter sequences. We obtained a statistically significant overrepresentation of TF sites distributed with the main period of 10.1-10.5 bp in the region -50 to +120 around the transcription start site and in few locations nearby. Correlation of the positioning of the TF sites with the nucleosomes is further reinforced by sequence-directed mapping of the nucleosomes, a method previously developed.