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Intracellular receptor concentration limits glucocorticoid-dependent enhancer activity.
J N Vanderbilt1, R Miesfeld, B A Maler
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0448.
Molecular Endocrinology (Baltimore, Md.)
|January 1, 1987
Summary
Glucocorticoid receptor (GR) levels directly impact gene transcription. Higher GR concentrations lead to greater chromatin changes and enhanced transcriptional responses at glucocorticoid response elements (GREs).
Area of Science:
- Molecular biology
- Genetics
- Cell biology
Background:
- The glucocorticoid receptor (GR) binds DNA at glucocorticoid response elements (GREs) to regulate gene transcription.
- GR acts as a hormone-dependent transcriptional enhancer, making it a key regulatory protein.
Purpose of the Study:
- To investigate the relationship between GR levels and transcriptional regulation.
- To determine if GR concentration is a limiting factor in glucocorticoid-induced gene expression.
Main Methods:
- Construction of cell lines with varying levels of GR expression.
- Analysis of chromatin structural alterations at GREs.
- Quantification of transcriptional responses to GR activation.
Main Results:
- The degree of chromatin alteration at GREs is proportional to cellular GR levels.
- Transcriptional responses are also proportional to the number of GR molecules per cell.
- GR appears to be a primary regulatory factor for tested glucocorticoid-responsive genes.
Conclusions:
- Cellular GR concentration is a critical determinant of transcriptional regulation at GREs.
- Other factors involved in GRE function and transcription initiation are likely in excess.
- This suggests a dose-dependent mechanism for GR-mediated gene activation.