DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival
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...
Saved in:
Published in | Cell Vol. 93; no. 4; pp. 531 - 541 |
---|---|
Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
15.05.1998
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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
GR
dim
are viable, revealing the in vivo relevance of DNA-binding-independent activities of the GR. |
---|---|
Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0092-8674 1097-4172 |
DOI: | 10.1016/S0092-8674(00)81183-6 |