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Open Access Highly Accessed Methodology article

Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

Emmitt R Jolly, Chen-Shan Chin, Ira Herskowitz and Hao Li*

Author Affiliations

Department of Biochemistry and Biophysics, University of California, San Francisco, 1700 4th Street, San Francisco, CA 94143, USA

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BMC Bioinformatics 2005, 6:275  doi:10.1186/1471-2105-6-275

Published: 18 November 2005

Abstract

Background

A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis.

Results

Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria.

Conclusion

We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.