title: FOG-1 represses GATA-1-dependent FcepsilonRI beta-chain transcription: transcriptional mechanism of mast-cell-specific gene expression in mice.
abstract: 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 reverse transcriptase-polymerase chain reaction (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 2 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 upregulated by coexpression of GATA-1, was significantly suppressed by coexpression 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 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 FcepsilonRI and beta-chain transcription. Finally, suppression of FOG-1 expression using an siRNA approach resulted in increased beta-chain promoter activity in Ba/F3. These results suggest that FOG-1 expression level regulates the GATA-1-dependent FcepsilonRI beta-chain promoter.
authors.affiliation: Atopy (Allergy) Research Center and Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tokura
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Nakano
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kanada
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D050982:GATA1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D017455:Receptors, IgE / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000276:immunology; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: C521907:Fc-epsilon receptor I beta-chain, mouse; D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D017455:Receptors, IgE; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse