Protein-DNA Array-based Identification of Transcription Factor Activities Regulated by Interaction with the Glucocorticoid Receptor

Abstract

The glucocorticoid receptor (GR) regulates gene expression by binding specific sequence elements within the promoters of target genes or by cross-talk with other transcription factors (TFs). For some TFs, interaction with the GR results in alteration of DNA binding and transcriptional regulation. We used a protein-DNA array, a system that facilitates simultaneous profiling of the activities of multiple transcription factors, to systematically examine the potential cross-talk of GRalpha with 149 TFs. Using this array, we identified several TFs, including IRF, E47, and COUP-TF, whose DNA binding activities were modulated by GRalpha. We then confirmed these results with in vitro electrophoretic mobility shift assays and in vivo reporter assays. In this study, IRF and E47 were identified as participants in GRalpha cross-talk for the first time. This new finding expands our understanding of the functional role of GRalpha in the context of gene expression regulation.