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Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene
Marinus F van Batenburg1, Hualing Li, J Annelies Polman
1Bioinformatics Laboratory, Academic Medical Center, Amsterdam, The Netherlands.
Plos One
|January 26, 2010
Summary
Researchers identified a new method to predict glucocorticoid target genes by looking for paired hormone response elements (HREs). This discovery reveals novel, tissue-specific glucocorticoid-responsive genes, enhancing our understanding of glucocorticoid actions.
Area of Science:
- Molecular Biology
- Genomics
- Endocrinology
Background:
- Glucocorticoids mediate effects through the glucocorticoid receptor (GR) binding to hormone response elements (HREs).
- Identifying direct glucocorticoid target genes in vivo remains a significant challenge in molecular biology.
Purpose of the Study:
- To develop a predictive criterion for identifying novel glucocorticoid-responsive genes in vivo.
- To discover tissue-specific glucocorticoid target genes and understand their regulatory mechanisms.
Main Methods:
- Developed a criterion based on paired HREs within 200 bp to predict hormone responsiveness.
- Applied this criterion to genomic regions upstream of genes.
- Validated predictions using multiple-tissue in situ hybridization in mice treated with corticosterone.
Main Results:
- The paired HRE criterion successfully predicted a substantial number of novel responsive genes.
- Six out of ten selected genes showed tissue-specific mRNA induction in response to corticosterone.
- Caveolin-1 was identified as a strongly responsive gene, with evidence of increased GR occupancy at its HRE pair.
Conclusions:
- The developed criterion effectively identifies novel, tissue-specific glucocorticoid target genes.
- This approach advances the understanding of glucocorticoid receptor regulation and gene expression.
- The findings provide insights into the permissive actions of glucocorticoids in various tissues.
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