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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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Submitted July 20, 2005
Accepted February 23, 2006
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
Atopy Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Atopy Research Center, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan; Department of Immunology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan
Biotechnology Research Center, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
* Corresponding author; email: chinishi{at}med.juntendo.ac.jp.
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 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 two 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 up-regulated by co-expression of GATA-1, was significantly suppressed by co-expression 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 can not bind FOG-1, was not affected by co-expression 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 a siRNA approach resulted in increased -chain promoter activity in Ba/F3. These results suggest FOG-1 that expression level regulates the GATA-1-dependent Fc RI -chain promoter.

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