Transcription factors regulating the erytnroid and megakaryocytic cell differentiation.

调节红细胞和巨核细胞分化的转录因子。

基本信息

批准号：
08670162
负责人：
MINEGISHI Naoko
金额：
$ 1.41万
依托单位：
University of Tsukuba (1997)Tohoku University (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670162/
关键词：
GATA-2 GATA-1 NF-E2p45 megakaryoyte erythrocyte hematopoietic stem cell erythropoietin thrombopoetin NF-E2p45 造血幹細胞 MPL 転写因子 NF-E2 ETSファミリー

项目摘要

In the erythroid and megakaryocytic lineage cells, GATA-1 and GATA-2 show overlapping expression. The gene targeting experiments demonstrate that GATA-2 is essential for the hematopoietic stem and progenitor cells while GATA-1 expression is required for the terminal differentiation of both erythrocytes and megakaryocytes. We investigated the gene expression of GATA factors on leukemic cells and the transcriptional regulation of GATA-2 gene. The results are as follows ;1), GATA-1 and GATA-2 were expressed concomitantly on the leukemic cells with megakaryocytic or erythroid surface markers. GATA-2 mRNA was also detected in the myelogenous leukemia cells without any megakaryocytic or erythroid features. GATA-2 expression in leukemic cells were correlated with the c-kit antigen expression. This finding was consistent with the reports that GATA-2 has distinct functions in hematopoietic stem/progenitor cells.2), Transcription of mouse GATA-2 gene was found to initiate from two distinct first … More exons, both of which encode entirely untranslated regions, while the remaining five exons are shared by each of the two divergent mRNAs. Reverse transcriptase-polymerase chain reaction analysis revealed that GATA-2 mRNA initiated at the upstream first exon (IS) in Sca-1+/c-kit+hematopoieticprogenitor cells, whereas mRNA initiated at the downstream first exon (IG) is expressed in all tissues and cell lines that express GATA-2. While the structure of the IG exon/promoter shows high similarity to those of the Xenopus and human GATA-2 gene, the IS exon/promoter has not been described previously. Sequences lying between-79 and -61 are found to be critical for the cell type-specific activity of the IS promoter, and the binding of transcription factors to this region were demonstrated.3), A transgene containing the IS promoter and 6 kbp upstream region diercted expression of a reporter gene recapitulated the GATA-2 expression in aorta-gonads-mesonephros region and in bone marrow cells. Deletion analysis of the upstream region of IS promoter localized a hematopoietic enhancer activity between 3.5 to 2.5 kbp upstream of the IS exon. This region contained one of the DNaseI hypersensitve sites. Less

在红细胞和巨核细胞谱系细胞中，GATA-1和GATA-2显示重叠的表达。基因靶向实验表明，GATA-2对于造血干细胞和祖细胞是必不可少的，而GATA-1表达对于红细胞和巨核细胞的终末分化是必需的。我们研究了GATA因子在白血病细胞上的基因表达和GATA-2基因的转录调节。结果如下; 1），GATA-1和GATA-2与巨核细胞或红细胞性表面标记在白血病细胞上同时表达。在没有任何巨核细胞或红斑特征的髓力性白血病细胞中也检测到GATA-2 mRNA。白血病细胞中的GATA-2表达与C-KIT抗原表达相关。这一发现与报道说，GATA-2在造血茎/祖细胞中具有不同的功能。逆转录酶 - 聚合酶链链反应分析表明，在SCA-1+/C-KIT+造血性造激素细胞中，在上游第一外显子（IS）启动的GATA-2 mRNA，而在下游第一外显子（Ig）中启动的mRNA始终以始终表达GATA-2的细胞线。尽管Ig外显子/启动子的结构与爪蟾和人GATA-2基因的结构表现出很高的相似性，但先前尚未描述IS外显子/启动子。 Sequences lying between-79 and -61 are found to be critical for the cell type-specific activity of the IS promoter, and the binding of transcription factors to this region were demonstrated.3), A transform containing the IS promoter and 6 kbp upstream region dieted expression of a reporter gene recapitulated the GATA-2 expression in aorta-gonads-mesonephros region and in bone marrow cells.对IS启动子上游区域的缺失分析定位于IS外显子上游的3.5至2.5 kbp之间的造血增强剂活性。该区域包含DNASEI高敏位点之一。较少的