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

Blood. 2006 Jul 1;108(1):262-9. doi: 10.1182/blood-2005-07-2878. Epub 2006 Mar 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • GATA1 Transcription Factor / antagonists & inhibitors*
  • GATA1 Transcription Factor / immunology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Mast Cells / immunology*
  • Mice
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / immunology
  • Nuclear Proteins / pharmacology*
  • Receptors, IgE / antagonists & inhibitors*
  • Receptors, IgE / genetics*
  • Receptors, IgE / immunology
  • Structure-Activity Relationship
  • Transcription Factors / biosynthesis
  • Transcription Factors / immunology
  • Transcription Factors / pharmacology*
  • Transcription, Genetic*


  • Fc-epsilon receptor I beta-chain, mouse
  • GATA1 Transcription Factor
  • Nuclear Proteins
  • Receptors, IgE
  • Transcription Factors
  • Zfpm1 protein, mouse