Identification and functional analysis of erythroid-specific genes regulated by heme

血红素调控的红系特异性基因的鉴定及功能分析

• 批准号: 18591038
• 负责人: HARIGAE Hideo
• 金额: $ 2.49万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591038/
• 关键词: heme; erythropoiesis; hematopoietic cell differentiation; transcriptional regulation

Erythroid cells synthesize and accumulate an enormous amount of hemoglobin in the late stage of their differentiation. It is possible that, in addition to hemoglobin synthesis, heme may also play another important role in the erythroid cell differentiation program. To identify erythroid- specific heme-regulated genes, we performed differential expression analysis between wild-type and heme-deficient erythroblasts, which had been prepared from wild-type and δ-aminolevulinate synthase (ALAS2)-null mouse ES cells, respectively. As a result, the final 4 were considered as the newly identified erythroid-specific heme-regulated genes. These 4 genes were uncoupling protein 2 (UCP2), nucleolar spindle-associated protein (NuSAP), cellular nucleic acid binding protein (CNBP), and a novel acetyltransferase-like protein. Among them, the function of Nusap was further analyzed. NuSAP mRNA was remarkably more abundant in the subset corresponding to immature erythroblasts (TER119^+CD71^<high>) than mature erythroblasts (TER119^+CD7^<low>), and it was significantly increased in TER119^+ cells from in vivo phlebotomized mice. These results suggested that NuSAP gene might contribute to the expansion of immature erythroblast pool. These findings thus suggest that heme may regulate a wide variety of genes in erythroid cell differentiation.

红细胞细胞在分化的后期合成并加剧了增强的血红蛋白。除血红蛋白合成外，血红素还可能在红系细胞分化程序中起另一个重要作用。为了鉴定红色特异性血红素调节的基因，我们在野生型和血红素缺乏成红细胞之间进行了差异表达分析，这些分别是由野生型和δ-氨基苯甲酸合酶（ALAS2）-Null小鼠ES细胞制备的。结果，最终4被视为新鉴定的红细胞特异性血红素调节基因。这4个基因是解偶联蛋白2（UCP2），核纺锤体相关蛋白（NUSAP），细胞核酸结合蛋白（CNBP）和一种新型的乙酰基转移酶样蛋白。其中，进一步分析了NUSAP的功能。与成熟的成年细胞（TER119^+CD71^<high>）相对应的子集中，NUSAP mRNA要比成熟的粉红色细胞（Ter119^+CD7^<low>）更丰富，并且它在Ter119^+细胞中从体内浮力浮游生物中的Ter119^+细胞中显着增加。这些结果表明，NUSAP基因可能有助于未成熟的红细胞池的扩张。因此，这些发现表明血红素可能调节红细胞分化的各种基因。

项目成果

Functional Analyses and Transcriptional Regulation of Mouse Nuclear Spindle-Associated Protein (NuSAP) Gene in Erythroid Cells : Essential Role of NF-Y

红系细胞中小鼠核纺锤体相关蛋白 (NuSAP) 基因的功能分析和转录调控：NF-Y 的重要作用

• 发表时间: 2006
• 期刊: British Journal of Haematology. 135
• 作者: Fujiwara T;Harigae H;Takahashi S;OkitsuY;Yokoyama H;Yamada FM;Ishizawa K;Kameoka J;Kaku M;Sasaki T
• 通讯作者: Sasaki T

Analyses of heme-regulated genes during erythroid differentiation

红系分化过程中血红素调节基因的分析

• 发表时间: 2007
• 作者: Fujiwara T;Okitsu Y;Ikura T;Takahashi S;Furuyama K;Igarashi K;Yamamoto M;Sassa S;Harigae H.
• 通讯作者: Harigae H.

Expression analyses and transcriptional regulation of mouse nucleolar spindle-associated protein gene in erythroid cells: essential role of NF-Y

• DOI: 10.1111/j.1365-2141.2006.06340.x
• 发表时间: 2006-11-01
• 期刊: BRITISH JOURNAL OF HAEMATOLOGY
• 影响因子: 6.5
• 作者: Fujiwara, Tohru;Harigae, Hideo;Sasaki, Takeshi
• 通讯作者: Sasaki, Takeshi

Analyses of Heme-regulated genes during erythroid differentiation.

红系分化过程中血红素调节基因的分析。

• 发表时间: 2007
• 作者: Fujiwara T;Harigae H;他5名
• 通讯作者: 他5名