Genomic approaches that aid in the identification of transcription factor target genes

Abstract

It is well-established that deregulation of the transcriptional activity of many different genes has been causatively linked to human diseases. In cancer, altered patterns of gene expression are often the result of the inappropriate expression of a specific transcriptional activator or repressor. Functional studies of cancer-specific transcription factors have relied upon the study of candidate target genes. More recently, gene expression profiling using DNA microarrays that contain tens of thousands of cDNAs corresponding to human mRNAs has allowed for a large-scale identification of genes that respond to increased or decreased levels of a particular transcription factor. However, such experiments do not distinguish direct versus indirect target genes. Coupling chromatin immunoprecipitation to microarrays that contain genomic regions (ChIP-chip) has provided investigators with the ability to identify, in a high-throughput manner, promoters directly bound by specific transcription factors. Clearly, knowledge gained from both types of arrays provides complementary Information, allowing greater confidence that a transcription factor regulates a particular gene. In this review, we focus on Polycomb group (PcG) complexes as an example of transcriptional regulators that are implicated In various cellular processes but about which very little is known concerning their target gene specificity. We provide examples of how both expression arrays and ChIP-chip microarray-based assays can be used to identify target genes of a particular PcG complex and suggest improvements in the application of array technology for faster and more comprehensive identification of directly regulated target genes.