[HTML][HTML] DNA binding of the glucocorticoid receptor is not essential for survival

HM Reichardt, KH Kaestner, J Tuckermann, O Kretz… - Cell, 1998 - cell.com
HM Reichardt, KH Kaestner, J Tuckermann, O Kretz, O Wessely, R Bock, P Gass, W Schmid…
Cell, 1998cell.com
Transcriptional regulation by the glucocorticoid receptor (GR) is essential for survival. Since
the GR can influence transcription both through 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 dimerization and therefore GRE-
dependent transactivation while functions that require cross-talk with other transcription …
Abstract
Transcriptional regulation by the glucocorticoid receptor (GR) is essential for survival. Since the GR can influence transcription both through 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 dimerization and therefore GRE-dependent transactivation while functions that require cross-talk with other transcription factors, such as transrepression of AP-1-driven genes, remain intact. In contrast to GR−/− mice, these mutants termed GRdim are viable, revealing the in vivo relevance of DNA-binding-independent activities of the GR.
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