THE ZINC FINGER TRANSCRIPTION FACTOR EGR-1 IS ESSENTIAL FOR AND RESTRICTS DIFFERENTIATION ALONG THE MACROPHAGE LINEAGE
THE ZINC FINGER TRANSCRIPTION FACTOR EGR-1 IS ESSENTIAL FOR AND RESTRICTS DIFFERENTIATION ALONG THE MACROPHAGE LINEAGE
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DOI：
10.1016/0092-8674(93)90660-i
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发表时间：
1993-01-29
期刊：
影响因子：
64.5
通讯作者：
LIEBERMANN, DA
中科院分区：
文献类型：
--
作者：
NGUYEN, HQ;HOFFMANLIEBERMANN, B;LIEBERMANN, DA
我们已经分离出髓细胞分化初级反应（MyD）基因的cDNA克隆，MyD基因在没有新生蛋白合成的情况下被激活，在人类髓细胞白血病HL-60细胞中诱导沿巨噬细胞或粒细胞谱系分化。巨噬细胞分化过程中表达的主要应答基因的一个cDNA克隆，编码锌指转录因子Egr-1。Egr-1基因在HL-60细胞中转录沉默，但在U-937和M1细胞中活跃，后者是巨噬细胞分化的预定细胞。培养基中的Egr-1反义寡聚物可阻断骨髓白血病细胞系和正常成髓细胞的巨噬细胞分化。组成性表达Egr-1转基因（HL-60Egr-1）的HL-60细胞可以诱导巨噬细胞分化，但不能诱导粒细胞分化。这些观察结果表明，Egr-1的表达对于巨噬细胞谱系中的成髓细胞分化至关重要，并限制了成髓细胞的分化。
We have isolated cDNA clones of myeloid differentiation primary response (MyD) genes, activated in the absence of de novo protein synthesis following induction for differentiation along either the macrophage or granulocyte lineage in human myeloblastic leukemia HL-60 cells. One cDNA clone of a primary response gene, expressed upon macrophage differentiation, encoded for Egr-1, a zinc finger transcription factor. The Egr-1 gene was observed to be transcriptionally silent in HL-60 cells, but active in U-937 and M1 cells, the latter two being predetermined for macrophage differentiation. Egr-1 antisense oligomers in the culture media blocked macrophage differentiation in both myeloid leukemia cell lines and normal myeloblasts. HL-60 cells constitutively expressing an Egr-1 transgene (HL-60Egr-1) could be induced for macrophage, but not granulocyte, differentiation. These observations indicate that expression of Egr-1 is essential for and restricts differentiation of myeloblasts along the macrophage lineage.