Many human cancers are caused by deregulation of specific transcription factors. To study the mechanisms by which transcriptional deregulation causes neoplasia, we are using a chromatin immunoprecipitation protocol to complement three different types of gene expression profiling. We first generated a weight matrix based on a set of known E2F binding sites and then used this weight matrix to search the genome for potential E2F binding sites. Using the chromatin immunoprecipitation assay, we confirmed the identification of a set of new E2F target genes. As a second approach, we have used the chromatin immunoprecipitation protocol to characterize the transcription complexes bound to β-catenin target genes that were identified by others using gene expression profiling of tissue culture cells. Using primary tumor samples, we show a direct recruitment of both β- and γ-catenin to certain cellular promoters. Finally we have used oligonucleotide microarrays and representational difference analysis to identify a set of genes that are highly upregulated in liver tumors. Our current goals are to identify common regulatory regions in the promoters that regulate these messenger RNAs specific to liver tumors and to characterize the components of the transcription complexes bound to these promoters using our chromatin immunoprecipitation protocol.