ISOLATION OF NF-E2-RELATED FACTOR-2 (NRF2), A NF-E2-LIKE BASIC LEUCINE-ZIPPER TRANSCRIPTIONAL ACTIVATOR THAT BINDS TO THE TANDEM NF-E2/AP1 REPEAT OF THE BETA-GLOBIN LOCUS-CONTROL REGION
ISOLATION OF NF-E2-RELATED FACTOR-2 (NRF2), A NF-E2-LIKE BASIC LEUCINE-ZIPPER TRANSCRIPTIONAL ACTIVATOR THAT BINDS TO THE TANDEM NF-E2/AP1 REPEAT OF THE BETA-GLOBIN LOCUS-CONTROL REGION
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DOI：
10.1073/pnas.91.21.9926
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发表时间：
1994-10-11
影响因子：
11.1
通讯作者：
KAN, YW
中科院分区：
文献类型：
--
作者：
MOI, P;CHAN, K;KAN, YW
位于 β-珠蛋白基因座控制区域的超敏感位点 2 赋予 β-珠蛋白簇基因高水平的表达。转录因子 AP1 和 NF-E2（分别是激活蛋白 1 和核因子红细胞 2）的共有序列的串联重复存在于过敏位点 2 内，并且是强增强子活性所必需的。该序列在体外和体内与普遍存在的 AP1 家族蛋白和最近克隆的红细胞特异性转录因子 NF-E2 结合。使用串联重复序列作为识别位点探针从 K562 细胞中筛选 lambda gt11 cDNA 表达文库，我们分离了几种 DNA 结合蛋白。在这里，我们报告了分离的克隆之一的特征。该基因被我们命名为 Nrf2（NF-E2 相关因子 2），在 2.2 kb 转录本中编码，并预测具有与 NF-E2 高度同源的基本亮氨酸拉链 DNA 结合域的 66 kDa 蛋白质。尽管 Nrf2 普遍表达，但不能排除该蛋白在介导红细胞中过敏位点 2 增强子活性中的作用。在这方面，Nrf2包含一个强大的酸性激活结构域，可能参与β-珠蛋白基因的转录刺激。
Hypersensitive site 2 located in the beta-globin locus control region confers high levels of expression to the genes of the beta-globin cluster. A tandem repeat of the consensus sequence for the transcription factors AP1 and NF-E2 (activating protein 1 and nuclear factor erythroid 2, respectively) is present within hypersensitive site 2 and is absolutely required for strong enhancer activity. This sequence binds, in vitro and in vivo, to ubiquitous proteins of the AP1 family and to the recently cloned erythroid-specific transcription factor NF-E2. Using the tandem repeat as a recognition site probe to screen a lambda gt11 cDNA expression library from K562 cells, we isolated several DNA binding proteins. Here, we report the characterization of one of the clones isolated. The gene, which we named Nrf2 (NF-E2-related factor 2), is encoded within a 2.2-kb transcript and predicts a 66-kDa protein with a basic leucine zipper DNA binding domain highly homologous to that of NF-E2. Although Nrf2 is expressed ubiquitously, a role of this protein in mediating enhancer activity of hypersensitive site 2 in erythroid cells cannot be excluded. In this respect, Nrf2 contains a powerful acidic activation domain that may participate in the transcriptional stimulation of beta-globin genes.