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Blood, 1 July 2006, Vol. 108, No. 1, pp. 262-269.
Prepublished online as a Blood First Edition Paper on March 7, 2006; DOI 10.1182/blood-2005-07-2878.
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IMMUNOBIOLOGY
FOG-1 represses GATA-1-dependent Fc RI -chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice
Keiko Maeda,
Chiharu Nishiyama,
Tomoko Tokura,
Hiroyasu Nakano,
Shunsuke Kanada,
Makoto Nishiyama,
Ko Okumura, and
Hideoki Ogawa
From the Atopy (Allergy) Research Center and Department of Immunology, Juntendo University School of Medicine, Tokyo; and Biotechnology Research Center, The University of Tokyo, Japan.
Cell-type-specific transcription of mouse high-affinity IgE receptor (Fc RI) -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 Fc RI -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 Fc RI -chain promoter. The expression levels of FOG-1, GATA-1, and -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 -chain-negative hematopoietic progenitor cell line Ba/F3 than in the -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 -chain promoter functioned in PT18 but not in Ba/F3 and that the transcription activity of the -chain promoter in PT18 was markedly suppressed by overexpression of FOG-1. Although the activity of the -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 ( -chain-, GATA-1-, and FOG-1-), the transactivation of the -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 Fc RI and -chain transcription. Finally, suppression of FOG-1 expression using an siRNA approach resulted in increased -chain promoter activity in Ba/F3. These results suggest that FOG-1 expression level regulates the GATA-1-dependent Fc RI -chain promoter. (Blood. 2006;108:262-269)

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