Kotkow K J, Orkin S H
Division of Hematology-Oncology, Children's Hospital, Dana Division of Hematology-Oncology, Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3514-8. doi: 10.1073/pnas.93.8.3514.
High-level globin expression in erythroid precursor cells depends on the integrity of NF-E2 recognition sites, transcription factor AP-1-like protein-binding motifs, located in the upstream regulatory regions of the alpha- and beta-globin loci. The NF-E2 transcription factor, which recognizes these sites, is a heterodimer consisting of (i) p45 NF-E2 (the larger subunit), a hematopoietic-restricted basic leucine zipper protein, and (ii) a widely expressed basic leucine zipper factor, p18 NF-E2, the smaller subunit. p18 NF-E2 protein shares extensive homology with the maf protooncogene family. To determine an in vivo role for p18 NF-E2 protein we disrupted the p18 NF-E2-encoding gene by homologous recombination in murine embryonic stem cells and generated p18 NF-E2-/- mice. These mice are indistinguishable from littermates throughout all phases of development and remain healthy in adulthood. Despite the absence of expressed p18 NF-E2, DNA-binding activity with the properties of the NF-E2 heterodimer is present in fetal liver erythroid cells of p18 NF-E2-/- mice. We speculate that another member of the maf basic leucine zipper family substitutes for the p18 subunit in a complex with p45 NF-E2. Thus, p18 NF-E2 per se appears to be dispensable in vivo.
红系前体细胞中的高水平珠蛋白表达取决于位于α和β珠蛋白基因座上游调控区域的NF-E2识别位点（转录因子AP-1样蛋白结合基序）的完整性。识别这些位点的NF-E2转录因子是一种异二聚体，由（i）p45 NF-E2（较大亚基），一种造血限制性碱性亮氨酸拉链蛋白，和（ii）一种广泛表达的碱性亮氨酸拉链因子p18 NF-E2（较小亚基）组成。p18 NF-E2蛋白与maf原癌基因家族具有广泛的同源性。为了确定p18 NF-E2蛋白在体内的作用，我们通过同源重组在小鼠胚胎干细胞中破坏了编码p18 NF-E2的基因，并产生了p18 NF-E2基因敲除小鼠。这些小鼠在发育的所有阶段与同窝小鼠没有区别，成年后仍然健康。尽管缺乏表达的p18 NF-E2，但p18 NF-E2基因敲除小鼠的胎儿肝脏红系细胞中存在具有NF-E2异二聚体特性的DNA结合活性。我们推测maf碱性亮氨酸拉链家族的另一个成员在与p45 NF-E2形成的复合物中替代了p18亚基。因此，p18 NF-E2本身在体内似乎是可有可无的。
