Nguyen H Q, Hoffman-Liebermann B, Liebermann D A
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Cell. 1993 Jan 29;72(2):197-209. doi: 10.1016/0092-8674(93)90660-i.
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.
我们已经分离出髓系分化初级反应（MyD）基因的cDNA克隆，这些基因在人髓性白血病HL-60细胞沿巨噬细胞或粒细胞谱系诱导分化后，在无从头蛋白质合成的情况下被激活。一个在巨噬细胞分化时表达的初级反应基因的cDNA克隆编码Egr-1，一种锌指转录因子。观察到Egr-1基因在HL-60细胞中处于转录沉默状态，但在U-937和M1细胞中活跃，后两者已预先确定向巨噬细胞分化。培养基中的Egr-1反义寡聚物可阻断髓系白血病细胞系和正常成髓细胞中的巨噬细胞分化。组成性表达Egr-1转基因的HL-60细胞（HL-60Egr-1）可被诱导向巨噬细胞而非粒细胞分化。这些观察结果表明，Egr-1的表达对于成髓细胞沿巨噬细胞谱系的分化至关重要且具有限制性。
