Cell-type specific transcription of mouse high-affinity IgE receptor (FcepsilonRI) beta-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 FcepsilonRI beta-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 FcepsilonRI beta-chain promoter. The expression levels of FOG-1, GATA-1, and beta-chain in each hematopoietic cell line were analyzed by RT-PCR and western blotting. FOG-1 expression was higher in the beta-chain negative hematopoietic progenitor cell line, Ba/F3, than in the beta-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 beta-chain promoter functioned in PT18 but not in Ba/F3 and that the transcription activity of the beta-chain promoter in PT18 was markedly suppressed by overexpression of FOG-1. Although the activity of the beta-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 [beta-chain(-), GATA-1(-), and FOG-1(-)), the transactivation of the beta-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 FcepsilonRI and beta-chain transcription. Finally, suppression of FOG-1 expression using a siRNA approach resulted in increased beta-chain promoter activity in Ba/F3. These results suggest FOG-1 that expression level regulates the GATA-1-dependent FcepsilonRI beta-chain promoter.