RGD Reference Report - GAR22: a novel target gene of thyroid hormone receptor causes growth inhibition in human erythroid cells. - Rat Genome Database

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GAR22: a novel target gene of thyroid hormone receptor causes growth inhibition in human erythroid cells.

Authors: Gamper, Ivonne  Koh, Ki-Ryang  Ruau, David  Ullrich, Katrin  Bartunkova, Jana  Piroth, Daniela  Hacker, Christine  Bartunek, Petr  Zenke, Martin 
Citation: Gamper I, etal., Exp Hematol. 2009 May;37(5):539-548.e4. doi: 10.1016/j.exphem.2009.02.002.
RGD ID: 12790653
Pubmed: PMID:19375645   (View Abstract at PubMed)
DOI: DOI:10.1016/j.exphem.2009.02.002   (Journal Full-text)


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.
MATERIALS AND METHODS: Stem cell factor/erythropoietin (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 downregulated genes, including distinct clusters associated with accelerated differentiation in response to treatment. Mining for T3-induced genes identified basic transcription element binding protein 1/Krüppel-like factor 9 (BTEB1/KLF9) 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.

Objects referenced in this article
Gene Gas2l1 growth arrest-specific 2 like 1 Rattus norvegicus

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