Research
Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeasts
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* Corresponding author: Michael B Eisen mbeisen@lbl.gov
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
2 Graduate Group in Biophysics, University of California, Berkeley, CA 94720, USA
3 Whitehead/MIT Center for Genome Research, Department of Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
4 Whitehead/MIT Center for Genome Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
5 Department of Genome Sciences, Life Sciences Division, Ernest Orlando Lawrence Berkeley National Lab, 1 Cyclotron Road, Berkeley, CA 94720, USA
6 Center for Integrative Genomics and Division of Genetics and Development, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Genome Biology 2003, 4:R43 doi:10.1186/gb-2003-4-7-r43
Published: 26 June 2003Abstract
Background
Transcriptional regulation in eukaryotes often involves multiple transcription factors binding to the same transcription control region, and to understand the regulatory content of eukaryotic genomes it is necessary to consider the co-occurrence and spatial relationships of individual binding sites. The determination of conserved sequences (often known as phylogenetic footprinting) has identified individual transcription factor binding sites. We extend this concept of functional conservation to higher-order features of transcription control regions.
Results
We used the genome sequences of four yeast species of the genus Saccharomyces to identify sequences potentially involved in multifactorial control of gene expression. We found 989 potential regulatory 'templates': pairs of hexameric sequences that are jointly conserved in transcription regulatory regions and also exhibit non-random relative spacing. Many of the individual sequences in these templates correspond to known transcription factor binding sites, and the sets of genes containing a particular template in their transcription control regions tend to be differentially expressed in conditions where the corresponding transcription factors are known to be active. The incorporation of word pairs to define sequence features yields more specific predictions of average expression profiles and more informative regression models for genome-wide expression data than considering sequence conservation alone.
Conclusions
The incorporation of both joint conservation and spacing constraints of sequence pairs predicts groups of target genes that are specific for common patterns of gene expression. Our work suggests that positional information, especially the relative spacing between transcription factor binding sites, may represent a common organizing principle of transcription control regions.