Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2
Redirecting differentiation of hematopoietic progenitors by a transcription factor, GATA-2
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DOI：
10.1182/blood-2005-06-2527
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发表时间：
2006-03-01
期刊：
影响因子：
20.3
通讯作者：
Nakano, T
中科院分区：
文献类型：
--
作者：
Kitajima, K;Tanaka, M;Nakano, T
加塔-2是一种锌指转录因子，对未成熟造血细胞的分化至关重要。我们通过四环素依赖的条件基因表达和使用OP 9基质细胞（OP 9系统）的小鼠胚胎干（ES）细胞体外造血分化的组合方法分析了加塔-2的功能。在巨噬细胞集落刺激因子（M-CSF）的存在下，OP 9系统诱导巨噬细胞分化。该系统中的加塔-2表达抑制巨噬细胞分化，并将造血分化的命运重定向到其他造血谱系。在第5天或第6天开始的加塔-2表达分别诱导巨核细胞或红细胞分化。PU.1是一种干扰加塔-2的造血转录因子，其表达水平似乎在向巨核细胞或红系分化中起关键作用。PU.1的转录受加塔-2与PU.1启动子区结合诱导的组蛋白乙酰化的影响。这项研究表明，加塔-2的功能是由PU. 1的表达，这反过来又是由加塔-2调节的上下文依赖性的方式修改。
GATA-2 is a zinc finger transcription factor essential for differentiation of immature hematopoietic cells. We analyzed the function of GATA-2 by a combined method of tetracycline-dependent conditional gene expression and in vitro hematopoietic differentiation from mouse embryonic stem (ES) cells using OP9 stroma cells (OP9 system). In the presence of macrophage colony-stimulating factor (M-CSF), the OP9 system induced macrophage differentiation. GATA-2 expression in this system inhibited macrophage differentiation and redirected the fate of hematopoietic differentiation to other hematopoietic lineages. GATA-2 expression commencing at day 5 or day 6 induced megalkaryocytic or erythroid differentiation, respectively. Expression levels of PU.1, a hematopoietic transcription factor that interferes with GATA-2, appeared to play a critical role in differentiation to megakaryocytic or erythroid lineages. Transcription of PU.1 was affected by histone acetylation induced by binding of GATA-2 to the PU.1 promoter region. This study demonstrates that the function of GATA-2 is modified in a context-dependent manner by expression of PU.1, which in turn is regulated by GATA-2.