title: DNA binding of the glucocorticoid receptor is not essential for survival.
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.
authors.affiliation: Division of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg.
authors.forename: H M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: K H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: J
authors.initials: J
authors.lastname: Tuckermann
authors.forename: O
authors.initials: O
authors.lastname: Kretz
authors.forename: O
authors.initials: O
authors.lastname: Wessely
authors.forename: R
authors.initials: R
authors.lastname: Bock
authors.forename: P
authors.initials: P
authors.lastname: Gass
authors.forename: W
authors.initials: W
authors.lastname: Schmid
authors.forename: P
authors.initials: P
authors.lastname: Herrlich
authors.forename: P
authors.initials: P
authors.lastname: Angel
authors.forename: G
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015672:Erythroid Precursor Cells; D005246:Feedback; D005786:Gene Expression Regulation / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010913:Pituitary-Adrenal System / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology; D014158:Transcription, Genetic
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D004247:DNA