TY - JOUR
T1 - Functional analysis reveals no transcriptional role for the glucocorticoid receptor β-isoform in zebrafish
AU - Chatzopoulou, Antonia
AU - Schoonheim, Peter J.
AU - Torraca, Vincenzo
AU - Meijer, Annemarie H.
AU - Spaink, Herman P.
AU - Schaaf, Marcel J.M.
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/5/15
Y1 - 2017/5/15
N2 - In humans, two splice variants of the glucocorticoid receptor (GR) existthe canonical α-isoform, and the β-isoform, which has been shown to have a dominant-negative effect on hGRα. Previously, we have established the occurrence of a GR β-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GRβ (zGRβ). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGRβ 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 zGRβ. Transcriptome analysis suggested transcriptional regulation of genes by zGRβ 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 β-isoform does not have a functional role in transcriptional regulation.
AB - In humans, two splice variants of the glucocorticoid receptor (GR) existthe canonical α-isoform, and the β-isoform, which has been shown to have a dominant-negative effect on hGRα. Previously, we have established the occurrence of a GR β-isoform in zebrafish, and in the present study we have investigated the functional role of the zebrafish GRβ (zGRβ). Reporter assays in COS-1 cells demonstrated a dominant-negative effect of zGRβ 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 zGRβ. Transcriptome analysis suggested transcriptional regulation of genes by zGRβ 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 β-isoform does not have a functional role in transcriptional regulation.
KW - Beta-isoform
KW - Corticosteroid
KW - Glucocorticoid receptor
KW - Microarray
KW - Transcriptome analysis
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85014121434&partnerID=8YFLogxK
U2 - 10.1016/j.mce.2017.02.036
DO - 10.1016/j.mce.2017.02.036
M3 - Article
C2 - 28242321
AN - SCOPUS:85014121434
SN - 0303-7207
VL - 447
SP - 61
EP - 70
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -