%0 Journal Article
%T Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis
%A Emmitt R Jolly
%A Chen-Shan Chin
%A Ira Herskowitz
%A Hao Li
%J BMC Bioinformatics
%D 2005
%I BioMed Central
%R 10.1186/1471-2105-6-275
%X 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.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.The availability of genome sequences for multiple species and large-scale gene expression data has led to the development of computational genomic approaches to transcriptional regulation. A challenge in the field is the accurate genome-wide identification of the regulatory targets of transcription factors (TF), which is a necessary step towards reconstructing cellular transcriptional networks. A number of functional genomic approaches have been developed to tackle this problem. For example, ChIP-chip (chromatin immunoprecipitation followed by hybridization to DNA chip) technology has been applied on a large scale to map the location of transcription factors in the yeast genome [1,2]. Gene expression profiling of cells in which a transcription factor is either overexpressed or deleted has also been used to identify targets [3-8]. While these are powerful approaches to systematically identifying target genes, they also have limitations. For example, ChIP-chip experiments performed under a specific condition may not identify the correct targets of a factor if that factor is not activated, or may only identify a subset of the target genes if the factor works with other TFs in a combinatorial fashion, and searching for a
%U http://www.biomedcentral.com/1471-2105/6/275