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首页> 外文期刊>Molecular and Cellular Biology >Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line.
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Erythroid-cell-specific properties of transcription factor GATA-1 revealed by phenotypic rescue of a gene-targeted cell line.

机译：通过靶向基因的细胞系的表型拯救揭示了转录因子GATA-1的类红细胞特有的特性。

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The zinc finger transcription factor GATA-1 is essential for erythropoiesis. In its absence, committed erythroid precursors arrest at the proerythroblast stage of development and undergo apoptosis. To study the function of GATA-1 in an erythroid cell environment, we generated an erythroid cell line from in vitro-differentiated GATA-1- murine embryonic stem (ES) cells. These cells, termed G1E for GATA-1- erythroid, proliferate as immature erythroblasts yet complete differentiation upon restoration of GATA-1 function. We used rescue of terminal erythroid maturation in G1E cells as a stringent cellular assay system in which to evaluate the functional relevance of domains of GATA-1 previously characterized in nonhematopoietic cells. At least two major differences were established between domains required in G1E cells and those required in nonhematopoietic cells. First, an obligatory transactivation domain defined in conventional nonhematopoietic cell transfection assays is dispensable for terminal erythroid maturation. Second, the amino (N) zinc finger, which is nonessential for binding to the vast majority of GATA DNA motifs, is strictly required for GATA-1-mediated erythroid differentiation. Our data lead us to propose a model in which a nuclear cofactor(s) interacting with the N-finger facilitates transcriptional action by GATA-1 in erythroid cells. More generally, our experimental approach highlights critical differences in the action of cell-specific transcription proteins in different cellular environments and the power of cell lines derived from genetically modified ES cells to elucidate gene function.
机译：锌指转录因子GATA-1对红细胞生成至关重要。在缺少它的情况下，定型的类红细胞前体会停滞在发育的成红细胞阶段并发生凋亡。为了研究GATA-1在类红细胞环境中的功能，我们从体外分化的GATA-1小鼠胚胎干细胞（ES）生成了类红细胞系。这些细胞被称为GATA-1- erythroid的G1E，以未成熟的成红细胞的形式增殖，但在恢复GATA-1功能后会完全分化。我们使用拯救G1E细胞中的最终类红细胞成熟作为严格的细胞测定系统，在其中评估以前在非造血细胞中表征的GATA-1域的功能相关性。在G1E细胞所需的结构域和非造血细胞所需的结构域之间建立了至少两个主要差异。首先，在常规的非造血细胞转染实验中定义的强制性反式激活结构域对于终末红系成熟是必不可少的。其次，GATA-1介导的类红细胞分化必须严格要求氨基（N）锌指，该指对于与绝大多数GATA DNA基序的结合而言是不必要的。我们的数据使我们提出了一个模型，其中与N指相互作用的核辅因子促进了GATA-1在红系细胞中的转录作用。更普遍地说，我们的实验方法强调了在不同细胞环境中细胞特异性转录蛋白的作用以及从基因修饰的ES细胞衍生的细胞系阐明基因功能的能力方面的关键差异。

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