In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis
In vivo requirements for GATA-1 functional domains during primitive and definitive erythropoiesis
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DOI：
10.1093/emboj/20.18.5250
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发表时间：
2001-09-17
期刊：
影响因子：
11.4
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
--
作者：
Shimizu, R;Takahashi, S;Yamamoto, M
GATA-1是红细胞/巨核细胞分化所必需的转录因子。为了研究GATA-1单个结构域对其活性的贡献，我们培育了表达GATA-1 N端或N端或c端锌指缺失的转基因小鼠（分别为Delta NT、Delta NF或Delta CF），并将其与GATA-1种系突变体（GATA-1.05）小鼠杂交。由于GATA-1基因位于x染色体上，雄性GATA-1突变体在胚胎期第12.5天死亡。Delta NF和Delta CF转基因均未能拯救GATA-1.051Y幼崽。然而，表达Delta NT而非Delta NF蛋白的转基因小鼠能够挽救最终的造血功能。在胚胎中，虽然Delta CF蛋白和缺失两个n端结构域的突变体（Delta NTNF）都不能支持原始红细胞生成，但两个独立的Delta NT和Delta NF突变体可以支持原始红细胞生成。因此，对GATA-1突变小鼠的谱系特异性转基因拯救揭示了GATA-1在原始和终末红细胞生成过程中特定结构域赋予的新特性，并证明NT和NF部分赋予GATA-1功能互补但可区分的特性。
GATA-1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. To investigate the contribution of individual domains of GATA-1 to its activity, transgenic mice expressing either an N-terminus, or an N- or C-terminal zinc finger deletion of GATA-1 (Delta NT, Delta NF or Delta CF, respectively) were generated and crossed to GATA-1 germline mutant (GATA-1.05) mice. Since the GATA-1 gene is located on the X-chromosome, male GATA-1 mutants die by embryonic day 12.5. Both Delta NF and Delta CF transgenes failed to rescue the GATA-1.051Y pups. However, transgenic mice expressing Delta NT, but not the Delta NF protein, were able to rescue definitive hematopoiesis. In embryos, while neither the Delta CF protein nor a mutant missing both N-terminal domains (Delta NTNF) was able to support primitive erythropoiesis, the two independent Delta NT and Delta NF mutants could support primitive erythropoiesis. Thus, lineage-specific transgenic rescue of the GATA-1 mutant mouse revealed novel properties that are conferred by specific domains of GATA-1 during primitive and definitive erythropoiesis, and demonstrate that the NT and NF moieties lend complementary, but distinguishable properties to the function of GATA-1.