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Proc Natl Acad Sci U S A. 2005 May 17;102(20):7079-84. Epub 2005 May 9.

De novo cis-regulatory module elicitation for eukaryotic genomes.

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  • 1Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27599, USA. gupta@bios.unc.edu


Transcription regulation is controlled by coordinated binding of one or more transcription factors in the promoter regions of genes. In many species, especially higher eukaryotes, transcription factor binding sites tend to occur as homotypic or heterotypic clusters, also known as cis-regulatory modules. The number of sites and distances between the sites, however, vary greatly in a module. We propose a statistical model to describe the underlying cluster structure as well as individual motif conservation and develop a Monte Carlo motif screening strategy for predicting novel regulatory modules in upstream sequences of coregulated genes. We demonstrate the power of the method with examples ranging from bacterial to insect and human genomes.

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