ECTOPIC EXPRESSION OF A CONDITIONAL GATA-2 ESTROGEN-RECEPTOR CHIMERA ARRESTS ERYTHROID-DIFFERENTIATION IN A HORMONE-DEPENDENT MANNER
ECTOPIC EXPRESSION OF A CONDITIONAL GATA-2 ESTROGEN-RECEPTOR CHIMERA ARRESTS ERYTHROID-DIFFERENTIATION IN A HORMONE-DEPENDENT MANNER
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DOI：
10.1101/gad.7.6.1097
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发表时间：
1993-06-01
影响因子：
10.5
通讯作者：
ZENKE, M
中科院分区：
文献类型：
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作者：
BRIEGEL, K;LIM, KC;ZENKE, M
GATA因子是真核生物中的一个转录调节蛋白家族，在其dna结合域具有广泛的同源性。GATA因子表达的一个神秘方面是，几个表面上具有相同dna结合位点特异性的GATA蛋白在红细胞中共表达。为了阐明单个GATA因子在红细胞生成中的作用，通过将GATA-1、GATA-2和GATA-3的条件等位基因融合到人雌激素受体（ER）的激素结合域，制备了GATA-1、GATA-2和GATA-3。这些GATA/ER嵌合因子在瞬时转染试验中被证明是激素诱导的反式激活蛋白。当外源性GATA-2/ER稳定导入原代红母细胞或条件转化红祖细胞时，外源性GATA-2/ER以雌激素依赖的方式促进增殖并抑制终末分化。这些表型效应特别归因于异位表达的GATA-2/ER的作用，因为表达外源性GATA-2的红母细胞在分化过程中构成性地受阻，而且表达Gal/ER或GATA-3/ER的红母细胞在分化过程中不会表现出激素反应性阻滞。因此，GATA-2转录因子似乎在调节早期红系祖细胞的自我更新能力中起作用。
The GATA factors are a family of transcriptional regulatory proteins in eukaryotes that share extensive homology in their DNA-binding domains. One enigmatic aspect of GATA factor expression is that several GATA proteins, which ostensibly share the same DNA-binding site specificity, are coexpressed in erythroid cells. To elucidate the roles of individual GATA factors in erythropoiesis, conditional alleles of GATA-1, GATA-2, and GATA-3 were prepared by fusing each of the factors to the hormone-binding domain of the human estrogen receptor (ER). These GATA/ER chimeric factors were shown to be hormone-inducible trans-activating proteins in transient transfection assays. When stably introduced into primary erythroblasts or conditionally transformed erythroid progenitors cells, exogenous GATA-2/ER promoted proliferation and inhibited terminal differentiation in an estrogen-dependent manner. These phenotypic effects are specifically attributable to the action of ectopically expressed GATA-2/ER because erythroblasts expressing exogenous GATA-2 are constitutively arrested in differentiation and because erythroid progenitors expressing either Gal/ER or GATA-3/ER do not display a hormone-responsive block in differentiation. Thus, the GATA-2 transcription factor appears to play a role in regulating the self-renewal capacity of early erythroid progenitor cells.