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


CONCLUSIONS
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.
Jolly
Emmitt R
ER
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA. emmitt.jolly@itsa.ucsf.edu
Chin
Chen-Shan
CS
Herskowitz
Ira
I
Li
Hao
H
D020816:Amino Acid Motifs; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000737:chemistry; D005189:False Positive Reactions; D016681:Genome, Fungal; D023281:Genomics / Q000379:methods*; D008957:Models, Genetic; D015233:Models, Statistical; D008962:Models, Theoretical; D016366:Open Reading Frames; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry; D012984:Software; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C097071:NDT80 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors