DNA-BINDING OF THE GLUCOCORTICOID RECEPTOR IS NOT ESSENTIAL FOR SURVIVAL

Transcriptional regulation by the glucocorticoid receptor (GR) is esse ntial for survival. Since the GR can influence transcription both thro ugh DNA-binding-dependent and -independent mechanisms, we attempted to assess their relative importance in vivo. In order to separate these modes of action, we introduced the point mutation A458T into the GR by gene targeting using the Cre/loxP system. This mutation impairs dimer ization and therefore GRE-dependent transactivation while functions th at require cross-talk with other transcription factors, such as transr epression of AP-1-driven genes, remain intact. In contrast to GR(-/-) mice, these mutants termed GR(dim) are viable, revealing the in vivo r elevance of DNA-binding-independent activities of the GR.