DNA binding of the glucocorticoid receptor is not essential for survival

Cell. 1998 May 15;93(4):531-41. doi: 10.1016/s0092-8674(00)81183-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Cells, Cultured
  • DNA / metabolism*
  • Dexamethasone / pharmacology
  • Erythroid Precursor Cells
  • Feedback
  • Gene Expression Regulation / physiology*
  • Glucocorticoids / pharmacology
  • Hypothalamo-Hypophyseal System / metabolism
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Pituitary-Adrenal System / metabolism
  • Point Mutation
  • Protein Binding
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • T-Lymphocytes / cytology
  • Transcription, Genetic


  • Glucocorticoids
  • Receptors, Glucocorticoid
  • Dexamethasone
  • DNA