FHL3 negatively regulates human high-affinity IgE receptor beta-chain gene expression by acting as a transcriptional co-repressor of MZF-1.

Abstract

The high-affinity IgE receptor FcepsilonRI plays a key role in triggering allergic reactions. We recently reported that human FcepsilonRI beta-chain gene expression was down-regulated by a transcription factor, MZF-1, through an element in the fourth intron. In the present study, we found that this transcriptional repression by MZF-1 required FHL3 (four and a half LIM domain protein 3) as a cofactor. Yeast two-hybrid and immunoprecipitation assays demonstrated that FHL3 bound MZF-1 in vitro and in vivo. Overexpression of FHL3 in KU812 cells suppressed the beta-chain promoter activity through the element in the fourth intron in an MZF-1-dependent manner. Furthermore, results from pull-down assays and gel-filtration chromatography employing nuclear extracts indicated that MZF-1 and FHL3 formed a complex of high molecular mass with some additional proteins in the nucleus. Granulocyte-macrophage colony-stimulating factor, which was reported to decrease FcepsilonRI expression, induced the accumulation of FHL3 in the nucleus, in accordance with the repressive role of FHL3 in beta-chain gene expression.

• Authors: Kyoko Takahashi, Chiyuki Matsumoto, Chisei Ra
• Journal: The Biochemical journal (Biochem J) Vol. 386 Issue Pt 1 Pg. 191-200 (Feb 15 2005) ISSN: 1470-8728 [Electronic] England
• PMID: 15453830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• DNA-Binding Proteins
• FHL3 protein, human
• Interleukin-3
• Intracellular Signaling Peptides and Proteins
• Kruppel-Like Transcription Factors
• LIM Domain Proteins
• MS4A2 protein, human
• MZF1 protein, human
• Receptors, IgE
• Recombinant Fusion Proteins
• Repressor Proteins
• Transcription Factors
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Cell Line, Tumor
• Cell Nucleus (chemistry)
• Chromatography, Gel
• DNA, Complementary (genetics)
• DNA-Binding Proteins (genetics, physiology)
• Down-Regulation (drug effects, physiology)
• Genes, Reporter
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Humans
• Interleukin-3 (pharmacology)
• Intracellular Signaling Peptides and Proteins (genetics, physiology)
• Introns (genetics)
• Kruppel-Like Transcription Factors
• LIM Domain Proteins
• Leukemia, Basophilic, Acute (pathology)
• Molecular Sequence Data
• Multigene Family
• Promoter Regions, Genetic (genetics)
• Protein Binding
• Protein Interaction Mapping
• Protein Structure, Tertiary
• Protein Transport
• Receptors, IgE (biosynthesis, genetics)
• Recombinant Fusion Proteins (physiology)
• Repressor Proteins (genetics, physiology)
• Saccharomyces cerevisiae (metabolism)
• Transcription Factors (genetics, physiology)
• Transcription, Genetic (drug effects, physiology)
• Transformation, Genetic
• Two-Hybrid System Techniques
• Zinc Fingers (genetics, physiology)