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| Status |
Public on Mar 21, 2014 |
| Title |
Selective enhancement and repression of glucocorticoid receptor signaling by coregulator Hic-5 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The glucocorticoid receptor (GR) recruits many coregulators via the well characterized AF2 interaction surface in the GR ligand binding domain, but LIM domain coregulator Hic-5 binds to the relatively uncharacterized tau2 activation domain in the hinge region of GR. Requirement of Hic-5 for glucocorticoid-regulated gene expression in U2OS osteosarcoma cells was defined by Hic-5 depletion and global gene expression analysis. Hic-5 depletion had selective and dramatic effects, positive and negative, on both activation and repression of GR target genes. For some hormone-induced genes, Hic-5 facilitated recruitment of the Mediator complex and RNA polymerase II. In contrast, many genes were not regulated by hormone until Hic-5 was depleted. On these genes Hic-5 acted at a very early step of the regulatory process, preventing efficient GR binding on enhancers, chromatin remodeling, and thus preventing glucocorticoid-driven transcriptional regulation. Overall, Hic-5 has selective and diverse roles on GR target genes, functioning as coactivator on some genes and corepressor on others, and either facilitating or opposing the glucocorticoid-driven actions of GR. Hic-5 exhibits multiple mechanisms of action, either regulating GR binding to DNA and chromatin remodeling, or facilitating later steps in transcription complex assembly.
We investigate the relationship between GR and Hic5 and identify classes of genes that respond differently when cells are induced with hormone and when Hic5 is knocked down
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| Overall design |
We knock down Hic-5 (TGFB1I1) in U2OS cells using siRNA (siHic5_2) along with nonspecific siRNA (shNS) and assay gene expression changes at 4 different time points of hormone treatment. We also include non-infected control (NI) as a second control at each time point.
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| Contributor(s) |
Chodankar R, Wu D, Siegmund KD, Stallcup MR |
| Citation(s) |
24591583 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 DK043093 |
Role of Coregulators in Steroid Hormone-Regulated Transcription |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Michael R Stallcup |
| R01 CA020535 |
Gene Regulation By Steroid Receptor Proteins |
University of California San Francisco |
KEITH Robert YAMAMOTO |
| P30 CA014089 |
Administrative Core |
UNIVERSITY OF SOUTHERN CALIFORNIA |
PETER A JONES |
| T32 CA009320 |
TRAINING PROGRAM IN VIRAL AND CHEMICAL CARCINOGENESIS |
UNIVERSITY OF SOUTHERN CALIFORNIA |
JOSEPH R LANDOLPH |
| T32 GM067587 |
Training in Cellular, Biochemical and Molecular Sciences |
UNIVERSITY OF SOUTHERN CALIFORNIA |
Michael R Stallcup |
|
| Submission date |
Apr 28, 2013 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Dai-Ying Wu |
| Organization name |
University of Southern California
|
| Department |
Biochemistry
|
| Lab |
Stallcup
|
| Street address |
1441 Eastlake Ave, NOR 6314
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90033 |
| Country |
USA |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA200630 |
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