Abstract
The availability of sequence specificities for a substantial fraction of yeast's transcription factors and comparative genomic algorithms for binding site prediction has made it possible to comprehensively annotate transcription factor binding sites genome-wide. Here we use such a genome-wide annotation for comprehensively studying promoter architecture in yeast, focusing on the distribution of transcription factor binding sites relative to transcription start sites, and the architecture of TATA and TATA-less promoters. For most transcription factors, binding sites are positioned further upstream and vary over a wider range in TATA promoters than in TATA-less promoters. In contrast, a group of ‘proximal promoter motifs’ (GAT1/GLN3/DAL80, FKH1/2, PBF1/2, RPN4, NDT80, and ROX1) occur preferentially in TATA-less promoters and show a strong preference for binding close to the transcription start site in these promoters. We provide evidence that suggests that pre-initiation complexes are recruited at TATA sites in TATA promoters and at the sites of the other proximal promoter motifs in TATA-less promoters. TATA-less promoters can generally be classified by the proximal promoter motif they contain, with different classes of TATA-less promoters showing different patterns of transcription factor binding site positioning and nucleosome coverage. These observations suggest that different modes of regulation of transcription initiation may be operating in the different promoter classes. In addition we show that, across all promoter classes, there is a close match between nucleosome free regions and regions of highest transcription factor binding site density. This close agreement between transcription factor binding site density and nucleosome depletion suggests a direct and general competition between transcription factors and nucleosomes for binding to promoters.
Highlights
Large-scale ChIP-chip and protein-microarray experiments, e.g. [1,2,3], have made it possible to identify the sequence specificities of a large number of transcription factors (TFs) in the yeast Saccharomyces cerevisiae
The sequence specificities of TFs are generally represented as position specific weight matrices (WMs) and using these WMs in combination with sophisticated comparative genomic algorithms for transcription factor binding site (TFBS) prediction, it is possible to obtain fairly comprehensive annotations of the TFBSs occurring across yeast promoters [4,5]
As described previously [19], we have developed sophisticated Bayesian probabilistic algorithms that, given a set of WMs and multiple alignments of intergenic sequences as input, predict TFBSs using explicit models of the evolution of TFBSs, neutrally evolving background sequences, and sequences that are under purifying selection for other reasons
Summary
Large-scale ChIP-chip and protein-microarray experiments, e.g. [1,2,3], have made it possible to identify the sequence specificities of a large number of transcription factors (TFs) in the yeast Saccharomyces cerevisiae. The sequence specificities of TFs are generally represented as position specific weight matrices (WMs) and using these WMs in combination with sophisticated comparative genomic algorithms for transcription factor binding site (TFBS) prediction, it is possible to obtain fairly comprehensive annotations of the TFBSs occurring across yeast promoters [4,5]. Having such comprehensive TFBS annotations available across promoters genome-wide in turn allows for a rigorous and quantitative study of the ‘grammar’ of this transcriptional regulatory code. We extend this work by comprehensively studying the positioning of TFBSs relative to TSS across all yeast promoters, and identify novel classes of nonTATA promoters which are characterized by the occurrence of alternative proximal promoter motifs
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