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| Status |
Public on Jul 31, 2008 |
| Title |
GAR22: A novel target gene of thyroid hormone receptor causes growth inhibition in human erythroid cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Objective: Thyroid hormone receptors (TRs) are ligand-dependent transcription factors with a major impact on erythroid cell development. Here we investigated TR activity on red cell gene expression and identified TR target genes. The impact of the TR target gene GAR22 (growth arrest specific 2 [GAS2]-related gene on chromosome 22) on red cell differentiation was determined.
Methods: SCF/Epo dependent red cell progenitors were differentiated in vitro in the presence or absence of thyroid hormone. Hormone-induced changes in gene expression were measured by a genome-wide approach with DNA microarrays. Ectopic expression of the TR target gene GAR22 was used to determine its impact on red cell differentiation.
Results: Ligand-activated TR effectively accelerated red cell progenitor differentiation in-vitro concomitantly with inducing growth arrest. We demonstrate that activated TR induced specific gene expression patterns of up- or down-regulated genes, including distinct clusters associated with accelerated differentiation in response to treatment. Mining for T3 induced genes identified BTEB1 (basic transcription element binding protein 1/Krüppel-like factor 9) and GAR22 as TR target genes. BTEB1/KLF9 is a known TR target gene while GAR22, initially identified as a putative tumor suppressor, represents a novel TR target gene. We demonstrate that ectopic GAR22 expression in red cell progenitors lengthens the cell cycle and causes growth inhibition, but leaves red cell gene expression unaffected.
Conclusion: This study identifies GAR22 as a novel and direct TR target gene. Our results suggest that hormone-induced GAR22 might represent an important trigger of growth inhibition induced by thyroid hormone in red cell progenitors.
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| Overall design |
13 hybridizations in two individual experiments.
Experiment 1:
1_SCF/Epo, 1_Epo/insulin(8h), 1_Epo/insulin(24h), 1_Epo/insulin(48h)
Experiment 2:
2_SCF/Epo, 2_Epo/insulin(8h), 2_Epo/insulin(24h), 2_Epo/insulin(48h)
2_Epo/insulin+T3(8h), 2_Epo/insulin+9cRA(8h)
2_Epo/insulin+T3+9cRA(8h), , 2_Epo/insulin+T3+9cRA(24h), 2_Epo/insulin+T3+9cRA(48h)
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| Contributor(s) |
Gamper I, Koh K, Ruau D, Ullrich K, Bartunkova J, Hacker C, Bartunek P, Zenke M |
| Citation(s) |
19375645 |
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| Submission date |
Apr 23, 2007 |
| Last update date |
Dec 13, 2018 |
| Contact name |
Martin Zenke |
| E-mail(s) |
Martin.Zenke@rwth-aachen.de
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| Phone |
+49-241-80 80760
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| Organization name |
Institute for Biomedical Engineering
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| Department |
Cell Biology
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| Street address |
Universitatsklinikum Aachen, RWTH
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| City |
Aachen |
| State/province |
NRW |
| ZIP/Postal code |
52074 |
| Country |
Germany |
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| Platforms (1) |
| GPL8300 |
[HG_U95Av2] Affymetrix Human Genome U95 Version 2 Array |
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| Samples (13)
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| GSM179757 |
Erythroid progenitor cells. SCF+Epo cells 0hr 1. |
| GSM180044 |
Erythroid progenitor cells. SCF+Epo cells 0hr 2. |
| GSM180045 |
Erythroid progenitor cells. Epo+insulin cells 8hr 1. |
| GSM180046 |
Erythroid progenitor cells. Epo+insulin cells 8hr 2. |
| GSM180047 |
Erythroid progenitor cells. Epo+insulin cells 24hr 1. |
| GSM180048 |
Erythroid progenitor cells. Epo+insulin cells 24hr 2. |
| GSM180049 |
Erythroid progenitor cells. Epo+insulin cells 48hr 1. |
| GSM180050 |
Erythroid progenitor cells. Epo+insulin cells 48hr 2. |
| GSM180051 |
Erythroid progenitor cells. Epo+insulin cells 8hr +T3 +9cRA 2. |
| GSM180052 |
Erythroid progenitor cells. Epo+insulin cells 24hr +T3 +9cRA 2. |
| GSM180053 |
Erythroid progenitor cells. Epo+insulin cells 48hr +T3 +9cRA 2. |
| GSM180054 |
Erythroid progenitor cells. Epo+insulin cells 8hr +9cRA 2. |
| GSM180056 |
Erythroid progenitor cells. Epo+insulin cells 8hr +T3 2. |
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| Relations |
| BioProject |
PRJNA100321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7579_RAW.tar |
110.5 Mb |
(http)(custom) |
TAR (of CEL, CHP, EXP) |
| Processed data provided as supplementary file |
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