NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development
NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development
复制标题
DOI：
10.1073/pnas.93.24.13943
复制
发表时间：
1996-11-26
影响因子：
11.1
通讯作者：
Kan, YW
中科院分区：
文献类型：
--
作者：
Chan, KM;Lu, RH;Kan, YW
β-珠蛋白基因的位点控制区由四个红系特异性超敏位点组成。超敏位点2已被证明是一个强大的增强子，并含有转录因子AP 1和NFE 2的串联重复序列（分别为活化蛋白1和核因子红细胞2），使用该核心序列作为探针，通过细菌表达筛选分离了p45-NFE 2，NRF 1，和NRF 2属于CNC（“cap”n“collar”）碱性区-亮氨酸拉链转录因子亚家族，其在特定区域如“CNC”和DNA结合和亮氨酸拉链结构域表现出很强的同源性。尽管红细胞特异性p45-NFE 2与珠蛋白基因调控有关，p45-NFE 2基因敲除的小鼠由于缺乏血小板而死亡，而存活的小鼠仅表现出轻度贫血。为了确定NRF 2的功能，我发现NRF 2在体内广泛表达，我们表征了小鼠NRF 2基因的基因组结构，通过同源重组在小鼠胚胎干细胞中破坏NRF 2基因（ES细胞），并产生NRF 2（-/-）小鼠，纯合子突变小鼠发育正常，不贫血，达到成年，并繁殖。
The locus control region of the beta-globin gene is composed of four erythroid-specific hypersensitive sites. Hypersensitive site 2 has been shown to be a powerful enhancer and contains a tandem repeat sequence for the transcription factors AP1 and NFE2 (activating protein 1 and nuclear factor erythroid 2, respectively), The human NRF2 (NFE2, related factor 2) has been isolated by bacterial expression screening using this core sequence as a probe, p45-NFE2, NRF1, and NRF2 belong to the CNC (''cap 'n' collar'') subfamily of the basic region-leucine zipper transcription factors, which exhibits strong homology at specific regions such as the ''CNC'' and the DNA binding and leucine zipper domains, Although the erythroid-specific p45-NFE2 has been implicated in globin gene regulation, p45-NFE2 null mice succumb to bleedings due to lack of platelets and those that survive exhibit only a mild anemia, To determine the function of NRF2, which me found to be widely expressed in vivo, we have characterized the genomic structure of the mouse NRF2 gene, disrupted the Nrf2 gene by homologous recombination in mouse embryonic stem cells (ES cells), and generated NRF2(-/-) mice, Homozygous mutant mice developed normally, were not anemic, reached adulthood, and reproduced, Our studies indicate that NRF2 is dispensable for mouse development.