The high-affinity IgE receptor FcεRI plays a key role in triggering allergic reactions. We recently reported that human FcεRI β-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 β-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 FcεRI expression, induced the accumulation of FHL3 in the nucleus, in accordance with the repressive role of FHL3 in β-chain gene expression.
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Research Article|
February 08 2005
FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1
Kyoko TAKAHASHI;
Kyoko TAKAHASHI
*Department of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, 30-1 Oyaguchi, Kami-machi, Itabashi-ku, Toyko 173-8610, Japan
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Chiyuki MATSUMOTO;
Chiyuki MATSUMOTO
*Department of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, 30-1 Oyaguchi, Kami-machi, Itabashi-ku, Toyko 173-8610, Japan
†Department of Dermatology, Surugadai Nihon University Hospital, 1-8-13 Kandasurugadai, Chiyoda-ku, Tokyo 101-8309, Japan
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Chisei RA
Chisei RA
1
*Department of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, 30-1 Oyaguchi, Kami-machi, Itabashi-ku, Toyko 173-8610, Japan
1To whom correspondence should be addressed (email fcericra@med.nihon-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
May 11 2004
Revision Received:
September 22 2004
Accepted:
September 24 2004
Accepted Manuscript online:
September 29 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 386 (1): 191–200.
Article history
Received:
May 11 2004
Revision Received:
September 22 2004
Accepted:
September 24 2004
Accepted Manuscript online:
September 29 2004
Citation
Kyoko TAKAHASHI, Chiyuki MATSUMOTO, Chisei RA; FHL3 negatively regulates human high-affinity IgE receptor β-chain gene expression by acting as a transcriptional co-repressor of MZF-1. Biochem J 15 February 2005; 386 (1): 191–200. doi: https://doi.org/10.1042/BJ20040775
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