Spatial Promoter Recognition Signatures May Enhance Transcription Factor Specificity in Yeast

Abstract

The short length and high degeneracy of sites recognized by DNA-binding transcription factors limit the amount of information they can carry, and individual sites are rarely sufficient to mediate the regulation of specific targets. Computational analysis of microbial genomes has suggested that many factors function optimally when in a particular orientation and position with respect to their target promoters. To investigate this further, we developed and trained spatial models of binding site positioning and applied them to the genome of the yeast Saccharomyces cerevisiae. We found evidence of non-random organization of sites within promoters, differences in binding site density, or both for thirty-eight transcription factors. We show that these signatures allow transcription factors with substantial differences in binding site specificity to share similar promoter specificities. We illustrate how spatial information dictating the positioning and density of binding sites can in principle increase the information available to the organism for differentiating a transcription factor’s true targets, and we indicate how this information could potentially be leveraged for the same purpose in bioinformatic analyses.

Intersecting transcription networks constrain gene regulatory evolution

“…Ste12 motifs were generated from general pheromone response gene intergenic regions pooled from all the species in a given clade. Each intergenic region was considered up to 600bp upstream of the start codon, a distance that is likely to capture functional Ste12 cis -regulatory sites 34 . The program MEME was used to find overrepresented sequences in these sets of intergenic regions, under conditions assuming zero to one binding site per intergenic region.…”