GATA-Dependent Expression of the Interleukin-1 Receptor-Related T1 Gene in Mast Cells
AUTOR(ES)
Gächter, Thomas
FONTE
American Society for Microbiology
RESUMO
The murine delayed-early serum-responsive gene T1 encodes glycoproteins of the interleukin-1 receptor family. Transcriptional initiation in fibroblasts is regulated by c-Fos and gives rise to a rare 5-kb mRNA and an abundant 2.7-kb mRNA. These transcripts are translated into a receptor-like membrane-anchored protein and a secreted protein consisting only of the ectodomain. In mast cells, T1 gene transcription is initiated 10.5 kb further upstream than in fibroblasts and gives rise predominantly to the 5-kb transcript under normal growth conditions. Here we demonstrate that calcium ionophore stimulation of mast cells resulted in an upregulation of T1 gene expression and a switch from the long to the short T1 transcript. This was paralleled by the disappearance of the receptor-type T1 protein on the mast cell surface and the secretion of large amounts of the truncated T1 protein. c-Fos and a T1 enhancer, which have previously been identified to be essential for T1 expression in fibroblasts, were not required for calcium ionophore-mediated T1 gene upregulation. Overexpression of the transcription factor GATA-1 in mast cells caused elevated T1 synthesis. Three GATA elements were identified in the minimal GATA-responsive mast cell promoter. Mutational analysis revealed that all three GATA elements are involved in T1 gene expression. Point mutations within the middle GATA element eliminated promoter activity completely, while mutations of the distal and proximal GATA binding sites reduced promoter strength by factors of 2 and 5, respectively. Exogenous expression of GATA-1 was not sufficient to activate the mast cell-specific promoter in NIH 3T3 fibroblasts.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=109117Documentos Relacionados
- GATA-dependent recruitment of MEF2 proteins to target promoters
- Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues.
- Expression of a Drosophila melanogaster acetylcholine receptor-related gene in the central nervous system.
- Molecular cloning and expression of an additional epidermal growth factor receptor-related gene.
- C766T low-density lipoprotein receptor-related protein 1 (LRP1) gene polymorphism and susceptibility to breast cancer