Glucocorticoid receptor (GR) beta has intrinsic, GRalpha-independent transcriptional activity.
The human glucocorticoid receptor (GR) gene produces C-terminal GRbeta and GRalpha isoforms through alternative use of specific exons 9beta and alpha, respectively. We explored the transcriptional activity of GRbeta on endogenous genes by developing HeLa cells stably expressing EGFP-GRbeta or EGFP. Microarray analyses revealed that GRbeta had intrinsic gene-specific transcriptional activity, regulating mRNA expression of a large number of genes negatively or positively. Majority of GRbeta-responsive genes was distinct from those modulated by GRalpha, while GRbeta and GRalpha mutually modulated each other's transcriptional activity in a subpopulation of genes. We did not observe in HCT116 cells nuclear translocation of GRbeta and activation of this receptor by RU 486, a synthetic steroid previously reported to bind GRbeta and to induce nuclear translocation. Our results indicate that GRbeta has intrinsic, GRalpha-independent, gene-specific transcriptional activity, in addition to its previously reported dominant negative effect on GRalpha-induced transactivation of GRE-driven promoters.
Kino
Tomoshige
T
Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892-1109, USA. kinot@mail.nih.gov
Manoli
Irini
I
Kelkar
Sujata
S
Wang
Yonghong
Y
Su
Yan A
YA
Chrousos
George P
GP
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D015735:Mifepristone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C103003:S100P protein, human; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D015735:Mifepristone