PUBLICATION
Functional analysis reveals no transcriptional role for the glucocorticoid receptor ?-isoform in zebrafish
- Authors
- Chatzopoulou, A., Schoonheim, P.J., Torraca, V., Meijer, A.H., Spaink, H.P., Schaaf, M.J.
- ID
- ZDB-PUB-170301-9
- Date
- 2017
- Source
- Molecular and Cellular Endocrinology 447: 61-70 (Journal)
- Registered Authors
- Meijer, Annemarie H., Schaaf, Marcel J. M., Schoonheim, Peter, Spaink, Herman P., Torraca, Vincenzo
- Keywords
- Beta-isoform, Corticosteroid, Glucocorticoid receptor, Microarray, Transcriptome analysis, Zebrafish
- Datasets
- GEO:GSE84906
- MeSH Terms
-
- Receptors, Glucocorticoid/metabolism*
- Transcription, Genetic*
- Animals, Genetically Modified
- Genes, Dominant
- Transcriptional Activation/genetics
- Chlorocebus aethiops
- Luciferases/metabolism
- Animals
- Zebrafish/embryology
- Zebrafish/genetics*
- Cell Line
- Gene Ontology
- COS Cells
- Green Fluorescent Proteins/metabolism
- Embryo, Nonmammalian/metabolism
- Protein Isoforms/metabolism
- PubMed
- 28242321 Full text @ Mol. Cell. Endocrinol.
Citation
Chatzopoulou, A., Schoonheim, P.J., Torraca, V., Meijer, A.H., Spaink, H.P., Schaaf, M.J. (2017) Functional analysis reveals no transcriptional role for the glucocorticoid receptor ?-isoform in zebrafish. Molecular and Cellular Endocrinology. 447:61-70.
Abstract
In humans, two splice variants of the glucocorticoid receptor (GR) exist: the canonical ?-isoform, and the ?-isoform, which has been shown to have a dominant-negative effect on hGR?. Previously, we have established the occurrence of a GR ?-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GR? (zGR?). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGR? but no such effect was observed in zebrafish PAC2 cells using induction of the fk506 binding protein 5 (fkbp5) gene as readout. Subsequently, we generated a transgenic fish line with inducible expression of zGR?. Transcriptome analysis suggested transcriptional regulation of genes by zGR? in this line, but further validation failed to confirm this role. Based on these results, its low expression level and its poor evolutionary conservation, we suggest that the zebrafish GR ?-isoform does not have a functional role in transcriptional regulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping