Transcription factors regulating normal and pathological platelet differentiation

调节正常和病理血小板分化的转录因子

• 批准号: 19390022
• 负责人: DOI Takefumi
• 金额: $ 12.06万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390022/
• 关键词: 血小板; 遺伝子発現制御; 分化; RUNX1; 転写因子; 巨核球; ES細胞; Hprt ターゲティング法; OP9

To understand the molecular mechanism for platelet production from hematopoietic stem cells, we focused on the Runx1 gene, which is closely related to familial platelet disorder (FPD). In the current study, RUNX1 is shown to bind to the promoter sequence of the PF4 gene, which is expressed only in platelet lineage, and cooperatively activate the promoter with ETS family proteins, ETS-1 and FLI-1. On the other hand, RUNX1 mutants found in the FPD patients could not activate the promoter. To understand the functional difference between wild type and mutant RUNX1 in physiological platelet differentiation, a novel ES cell differentiation system was established, in which exogenous genes can be overexpressed only in platelet lineage

为了了解造血干细胞产生血小板的分子机制，我们将重点放在与家族性血小板疾病（FPD）密切相关的Runx 1基因上。在目前的研究中，RUNX 1被证明与PF 4基因的启动子序列结合，该基因仅在血小板谱系中表达，并与ETS家族蛋白ETS-1和FLI-1协同激活启动子。另一方面，在FPD患者中发现的RUNX 1突变体不能激活启动子。为了了解野生型和突变型RUNX 1在生理性血小板分化中的功能差异，我们建立了一种新的ES细胞分化系统，其中外源基因只能在血小板谱系中过表达

项目成果

A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo

• DOI: 10.1182/blood-2008-01-135079
• 发表时间: 2008-09-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Okada, Yoshiaki;Jin, Enjing;Aird, William C.
• 通讯作者: Aird, William C.

A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium

• DOI: 10.1161/01.res.0000269779.10644.dc
• 发表时间: 2007-06-22
• 期刊: CIRCULATION RESEARCH
• 影响因子: 20.1
• 作者: Okada, Yoshiaki;Yano, Kiichiro;Aird, William C.
• 通讯作者: Aird, William C.

Differential context-dependent effects of friend of GATA-1 (FOG-1) on mast-cell development and differentiation.

• DOI: 10.1182/blood-2007-08-104489
• 发表时间: 2008-02
• 期刊: Blood
• 影响因子: 20.3
• 作者: Daijiro Sugiyama;Makoto Tanaka;K. Kitajima;Jie Zheng;Hilo Yen;T. Murotani;A. Yamatodani;T. Nakano

A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice.

• DOI: 10.1111/j.1538-7836.2009.03501.x
• 发表时间: 2009-08
• 期刊: Journal of thrombosis and haemostasis : JTH
• 作者: Liu J;Kanki Y;Okada Y;Jin E;Yano K;Shih SC;Minami T;Aird WC
• 通讯作者: Aird WC

Associations between PIWI proteins and TDRD1/MTR-1 are critical for integrated subcellular localization in murine male germ cell

PIWI 蛋白和 TDRD1/MTR-1 之间的关联对于小鼠雄性生殖细胞的整合亚细胞定位至关重要

• 发表时间: 2009
• 期刊: Genes. Cells Vol.14
• 作者: K. Kojima;S. Kuramochi-Miyagawa;S. Chuma;T. Tanaka;N. Nakatsuji;T. Kimura;T. Nakano
• 通讯作者: T. Nakano