EXTRACTING REGULATORY SITES FROM THE UPSTREAM REGION OF YEAST GENES BY COMPUTATIONAL ANALYSIS OF OLIGONUCLEOTIDE FREQUENCIES

We present here a simple and fast method allowing the isolation of DNA binding sites for transcription factors from families of coregulated genes, with results illustrated in Saccharomyces cerevisiae. Although conceptually simple, the algorithm proved efficient for extracting, fr om most of the yeast regulatory families analyzed, the upstream regula tory sequences which had been previously found by experimental analysi s. Furthermore, putative new regulatory sites are predicted within ups tream regions of several regulons. The method is based on the detectio n of over-represented oligonucleotides. A specificity of this approach is to define the statistical significance of a site based on tables o f oligonucleotide frequencies observed in all non-coding sequences fro m the yeast genome. In contrast with heuristic methods, this oligonucl eotide analysis is rigorous and exhaustive. Its range of detection is however limited to relatively simple patterns: short motifs with a hig hly conserved core. These features seem to be shared by a good number of regulatory sites in yeast. This, and similar methods, should be inc reasingly required to identify unknown regulatory elements within the numerous new coregulated families resulting from measurements of gene expression levels at the genomic scale. All tools described here are a vailable on the web at the site http:// pan.cifn.unam.mx/Computational _Biology/yeast-tools (C) 1998 Academic Press.