Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells
Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells
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DOI：
10.1532/ijh97.06020
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发表时间：
2006-07-01
影响因子：
2.1
通讯作者：
Sasaki, Takeshi
中科院分区：
文献类型：
--
作者：
Harigae, Hideo;Okitsu, Yoko;Sasaki, Takeshi
加塔转录因子在造血过程中起重要作用。加塔-2在干细胞和祖细胞中表达，并被推测控制这些细胞的增殖和维持这些细胞的不成熟。为了检查加塔-2的功能是否根据分化阶段而变化，我们建立了K562的加塔-2过表达亚克隆，K562是一种定向于红系的白血病细胞系。通过加塔-2表达水平的增加，与对照细胞相比，包括α-、β-和γ-珠蛋白的红系特异性基因的表达水平增加，而加塔-1的表达水平不变。流式细胞术检测转铁蛋白受体的表达在加塔-2过表达的K562细胞中也增加。另外，过表达加塔-2的K562细胞的血红素含量比对照细胞高2倍以上。染色质免疫沉淀分析显示，在加塔-2过表达的K562细胞中，与α-珠蛋白LCR中的加塔元件结合的加塔-2蛋白增加。这些发现表明，当在红系定型细胞中表达时，加塔-2可以诱导红系特异性基因而不与加塔-1竞争，因此进一步表明时间和空间调节对于显示加塔-2的特异性功能可能是重要的。
GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.