Whole-genome discovery of transcription factor binding sites by network-level conservation

Moshe Pritsker, Yir Chung Liu, Michael Beer, Saeed Tavazoie

Research output: Contribution to journalArticle

Abstract

Comprehensive identification of DNA cis-regulatory elements is crucial for a predictive understanding of transcriptional network dynamics. Strong evidence suggests that these DNA sequence motifs are highly conserved between related species, reflecting strong selection on the network of regulatory interactions that underlie common cellular behavior. Here, we exploit a systems-level aspect of this conservation-the network-level topology of these interactions-to map transcription factor (TF) binding sites on a genomic scale. Using network-level conservation as a constraint, our algorithm finds 71% of known TF binding sites in the yeast Saccharomyces cerevisiae, using only 12% of the sequence of a phylogenetic neighbor. Most of the novel predicted motifs show strong features of known TF binding sites, such as functional category and/or expression profile coherence of their corresponding genes. Network-level conservation should provide a powerful constraint for the systematic mapping of TF binding sites in the larger genomes of higher eukaryotes.

Original languageEnglish (US)
Pages (from-to)99-108
Number of pages10
JournalGenome Research
Volume14
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Transcription Factors
Binding Sites
Genome
Nucleotide Motifs
Gene Regulatory Networks
Eukaryota
Saccharomyces cerevisiae
Yeasts
DNA
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Whole-genome discovery of transcription factor binding sites by network-level conservation. / Pritsker, Moshe; Liu, Yir Chung; Beer, Michael; Tavazoie, Saeed.

In: Genome Research, Vol. 14, No. 1, 01.2004, p. 99-108.

Research output: Contribution to journalArticle

Pritsker, Moshe ; Liu, Yir Chung ; Beer, Michael ; Tavazoie, Saeed. / Whole-genome discovery of transcription factor binding sites by network-level conservation. In: Genome Research. 2004 ; Vol. 14, No. 1. pp. 99-108.
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