Regulation of the high affinity IgE receptor β-chain gene expression

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The high affinity IgE receptor (FcεRI) plays a key role in triggering IgE-mediated allergic reaction. FcεRI consists of three different subunits, of which the β-chain regulates both intracellular signals and cell surface expression of FcεRI.We previously reported that the transcription factor MZF-1 repressed the β-chain gene expression through an element in the fourth intron by forming a high molecular weight complex including FHL3. It was also revealed that GM-CSF induced nuclear translocation of FHL3 in addition to upregulation of MZF-1.In this study, we at first screened a human cDNA library for proteins forming a ternary complex with MZF-1 and FHL3 to identify the constituents of the large regulatory complex binding to the element in the fourth intron. NFY which was reported to bind histone deacetylases (HDACs) was identified as candidate and was shown to interact with the fourth intron region of β-chain gene by a ChIP assay. Furthermore, HDACs which were reported to bind NFY was demonstrated to interact with the fourth intron region of β-chain gene. In a human mast cell line HMC-1cultured with GM-CSF, both β-chaingene expression and acetylation of histones interacting with the fourth intron region of β-chain gene was decreased. Collectively, these results indicated that HDACs, which were recruited to β-chain gene through the element in the fourth intron by MZF-1/FHL3/NFY, repressed β-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 β-chain gene expression in differentiating hematopoietic cells but also the repression of b-chain gene expression in the peripheral cells under specific circumstances.