The binding of transcription factors to specific DNA sequences determines the populations of target genes to be expressed and how their transcription is regulated. Mapping transcription factor-binding sites and identifying these target genes remains an imposing obstacle to understanding the complex nature of gene regulatory networks. Furthermore, identification of the sites bound by transcription factors under different activation conditions is necessary to fully address many questions regarding transcriptional regulation. Of particular interest is how the selection of binding sites varies after activation by different stimuli. Do interactions between cooperating transcription factors affect their binding site selection? Do these interactions completely redirect the binding of existing factors to new sites or only a subset of sites? Do additional new sites become available under new conditions? Ultimately, what is the effect on the transcriptional regulation of target genes? With the advances in genomics technologies, we can now explore these and many other questions regarding the intricate circuitry of transcriptional regulation.The STAT (signal transducer and activator of transcription) family of proteins mediates the transcriptional responses to many cytokines and growth factors and is a useful system for studying inducible gene regulation. Different stimuli trigger the JAK-STAT pathway to phosphorylate latent, cytosolic STAT monomers, allowing them to form homo-and/or heterodimers. These stimuli induce the formation of different STAT dimer combinations, which in turn bind to specific DNA target sites and regulate the transcription of genes involved in proliferation, differentiation, apoptosis, antiviral response, inflammation, and immune response (for reviews, see Ramana et al. 2000;Levy and Darnell 2002). Since their discovery more than 10 years ago, much research has focused on understanding STAT activation, regulation, structure, and the phenotypic effects of their absence. However, significantly less progress has been made toward identifying the specific STAT-regulated