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

高亲和力 IgE 受体 β 链基因表达的调控

• 批准号: 17607013
• 负责人: TAKAHASHI Kyoko
• 金额: $ 2.24万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17607013/
• 关键词: allergy; IgE receptor; gene; expression; mast cell; 遺伝子発現

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.

高亲和力IgE受体（FcεRI）在IgE介导的变态反应中起关键作用。FcεRI由三个不同的亚基组成，其中β链既调控FcεRI的胞内信号，又调控FcεRI的细胞表面表达，我们曾报道转录因子MZF-1通过第四内含子中的元件与FHL 3形成高分子量复合物，抑制β链基因的表达。本研究首先从人cDNA文库中筛选与MZF-1和FHL 3形成三元复合物的蛋白质，以鉴定与第四内含子元件结合的大型调控复合物的组成成分。NFY是一个与组蛋白脱乙酰酶（HDACs）结合的蛋白，ChIP实验表明它与β链基因第四内含子区相互作用。此外，已报道的与NFY结合的HDAC被证明与β链基因的第四内含子区相互作用。在人肥大细胞系HMC-1中，GM-CSF可抑制β链基因的表达，并抑制与β链基因第四内含子区相互作用的组蛋白的乙酰化。总之，这些结果表明，在GM-CSF存在下，通过MZF-1/FHL 3/NFY第四内含子中的元件募集到β链基因的HDAC通过组蛋白的去乙酰化抑制β链基因的转录。这些机制不仅涉及分化造血细胞中β链基因表达的细胞类型特异性抑制，而且还涉及在特定情况下外周细胞中b链基因表达的抑制。

项目成果

C/EBPa functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (FcaR, CD89) promoter.

C/EBPα在功能上和物理上与GABP相互作用以激活人骨髓IgA Fc受体(FcaR、CD89)启动子。

• 发表时间: 2005
• 期刊: Blood 106
• 作者: Shimokawa T;Ra C.
• 通讯作者: Ra C.

Dapsone suppresses human neutrophil superoxide production and elas tase release by a calcium-dependent manner.

氨苯砜通过钙依赖性方式抑制人中性粒细胞超氧化物的产生和弹性蛋白酶的释放。

• 发表时间: 2005
• 期刊: Br.J.Dermatol. (印刷中)
• 作者: Suda T;Suzuki Y;Matsui T;Inoue T;Niide O;Yoshimaru T;Suzuki H;Ra C;Ochiai T.
• 通讯作者: Ochiai T.

Molecular mechanisms for transcriptional regulation of human high-affinity IgE receptor β-chain gene induced by GM-CSF.

GM-CSF诱导人高亲和力IgE受体β链基因转录调控的分子机制。

• 发表时间: 2006
• 期刊: J. Immunol. 177
• 作者: Takahashi K;Hayashi N;Kaminogawa S;Ra C
• 通讯作者: Ra C

Common and distinct signaling cascades in the production of TNF-aand IL-13 induced by LPS in RBL-2H3 cells.

RBL-2H3 细胞中 LPS 诱导产生 TNF-α 和 IL-13 过程中常见且不同的信号级联。

• 发表时间: 2005
• 期刊: Clin. Exp. Allergy 35
• 作者: Gon Y;Nunomura S;Ra C.
• 通讯作者: Ra C.

LDOC1, a novel MZF-1-interacting protein, induces apoptosis

• DOI: 10.1016/j.febslet.2004.12.030
• 发表时间: 2005-01-31
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Inoue, M;Takahashi, K;Ra, C
• 通讯作者: Ra, C