Molecular mechanisms for transcriptional regulation of human high-affinity IgE receptor beta-chain gene induced by GM-CSF.
The beta-chain of the high-affinity receptor for IgE (FcepsilonRI) plays an important role in regulating activation of FcepsilonRI-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 beta-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 beta-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 beta-chain gene. In a human mast cell line HMC-1 cultured with GM-CSF, both beta-chain expression and acetylation of histones interacting with the fourth intron region of the beta-chain gene were decreased. Collectively, these results indicated that HDACs, which were recruited to the beta-chain gene through the element in the fourth intron by MZF-1/FHL3/NFY, repressed beta-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 beta-chain gene expression in differentiating hemopoietic cells but also the repression of beta-chain gene expression in the peripheral cells under specific circumstances.
Takahashi
Kyoko
K
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.
Hayashi
Natsuko
N
Kaminogawa
Shuichi
S
Ra
Chisei
C
D000107:Acetylation; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007438:Introns; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; D008407:Mast Cells / Q000378:metabolism*; D017455:Receptors, IgE / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D023081:CCAAT-Binding Factor; D004268:DNA-Binding Proteins; C117563:FHL3 protein, human; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D060588:LIM Domain Proteins; C502447:MS4A2 protein, human; C085969:MZF1 protein, human; D017455:Receptors, IgE; D014157:Transcription Factors; C402244:nuclear factor Y; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006655:Histone Deacetylases