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Genome Biology volume 3, Article number: spotlight-20020712-01 (2002)
Deciphering the cis-regulatory code hidden within genome sequences is a formidable challenge for the post-genomic era. In the Early Edition of the Proceedings of the National Academy of Sciences, Rebeiz et al. report the creation of a computational method for identifying potential cis-regulatory modules and target genes. Their algorithm, called SCORE (Site Clustering Over Random Expectation), evaluates statistically significant enrichment for clusters of binding sites of a particular transcription factor within genome sequence. Rebeiz et al. validated this approach by looking for enhancers regulated by Suppressor of Hairless [Su(H)], a component of the Notch signalling pathway in Drosophila. They found over 15,000 potential Su(H)-binding sites in the Drosophila genome and used the well-known observation that bona fide binding sites are often clustered to identify potentially significant binding sites, within clusters. Many of these clusters fall near genes that are regulated by Notch signalling. Rebeiz et al. provide experimental support for their results by showing that one of the clusters regulates Su(H)-dependent expression.
Proceedings of the National Academy of Sciences, [http://www.pnas.org]
SCORE: A computational approach to the identification of cis-regulatory modules and target genes in whole-genome sequence data , [http://www.pnas.org/cgi/doi/10.1073/pnas.152320899]
Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity.