FOG-1 represses GATA-1-dependent FcϵRI β-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice

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Abstract
Cell-type-specific transcription of mouse high-affinity IgE receptor (FcϵRI) β-chain is positively regulated by the transcription factor GATA-1. Although GATA-1 is expressed in erythroid cells, megakaryocytes, and mast cells, the expression of mouse FcϵRI β-chain is restricted to mast cells. In the present study, we characterized the role of GATA-associated cofactor FOG-1 in the regulation of the FcϵRI β-chain promoter. The expression levels of FOG-1, GATA-1, and β-chain in each hematopoietic cell line were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. FOG-1 expression was higher in the β-chain-negative hematopoietic progenitor cell line Ba/F3 than in the β-chain-positive mast cell line PT18. By contrast, GATA-1 expression was similar when comparing the 2 cell lines. A transient reporter assay demonstrated that the β-chain promoter functioned in PT18 but not in Ba/F3 and that the transcription activity of the β-chain promoter in PT18 was markedly suppressed by overexpression of FOG-1. Although the activity of the β-chain promoter, which was upregulated by coexpression of GATA-1, was significantly suppressed by coexpression of FOG-1 in the simian kidney CV-1 cells (β-chain-, GATA-1-, and FOG-1-), the transactivation of the β-chain promoter by the GATA-1 mutant V205G, which cannot bind FOG-1, was not affected by coexpression of FOG-1. Further, overexpression of FOG-1 in PT18 resulted in decreases in cell surface expression of FcϵRI and β-chain transcription. Finally, suppression of FOG-1 expression using an siRNA approach resulted in increased β-chain promoter activity in Ba/F3. These results suggest that FOG-1 expression level regulates the GATA-1-dependent FcϵRI β-chain promoter. (Blood. 2006;108:262-269)