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-Chain Gene Induced by GM-CSF1
* Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan;
Nihon University College of Bioresource Sciences, Kanagawa, Japan; and
Department of Applied Biological Chemistry, Tamagawa University, Tokyo, Japan
The 
-chain of the high-affinity receptor for IgE (Fc
RI) plays an important role in regulating activation of FcRI-expressing cells such as mast cells in allergic reactions. We already reported that the transcription factor myeloid zinc finger (MZF) 1 which formed a high m.w. complex including four and a half LIM-only protein (FHL)3 in the nucleus repressed human -chain gene expression through an element in the fourth intron. We also found that GM-CSF induced expression of MZF-1 and nuclear translocation of FHL3. We screened a human cDNA library and identified NFY which was reported to bind histone deacetylases (HDACs) as a constituent of the complex. The C-subunit of NFY was demonstrated to form a ternary complex with MZF-1/FHL3 and interact with a -chain gene region including the element in the fourth intron. HDAC1 and HDAC2 were also shown to interact with the fourth intron region of the -chain gene. In a human mast cell line HMC-1 cultured with GM-CSF, both -chain expression and acetylation of histones interacting with the fourth intron region of the -chain gene were decreased. Collectively, these results indicated that HDACs, which were recruited to the -chain gene through the element in the fourth intron by MZF-1/FHL3/NFY, repressed -chain gene transcription by deacetylation of histones in the presence of GM-CSF. These mechanisms will be involved in not only the cell type-specific repression of -chain gene expression in differentiating hemopoietic cells but also the repression of -chain gene expression in the peripheral cells under specific circumstances.
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1 This work was supported in part by a Grant-in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Chisei Ra, Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. E-mail address: fcericra{at}med.nihon-u.ac.jp
3 Abbreviations used in this paper: MZF, myeloid zinc finger; FHL, four and a half LIM-only protein; HDAC, histone deacetylase; BD, binding domain; ADH, alcohol dehydrogenase; HA, hemagglutinin; AD, activation domain; ChIP, chromatin immunoprecipitation.
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