Different Transcription Factors Regulate nestin Gene Expression during P19 Cell Neural Differentiation and Central Nervous System Development
Different Transcription Factors Regulate nestin Gene Expression during P19 Cell Neural Differentiation and Central Nervous System Development
复制标题
不同转录因子在 P19 细胞神经分化和中枢神经系统发育过程中调节巢蛋白基因表达
DOI：
10.1074/jbc.m805632200
复制
发表时间：
2009-03-20
影响因子：
4.8
通讯作者：
Jing, Naihe
中科院分区：
文献类型：
--
作者：
Jin, Zhigang;Liu, Li;Jing, Naihe
巢蛋白是神经前体细胞的分子标记物。大鼠和人类的巢蛋白基因在其第二内含子中具有中枢神经系统特异的增强子。然而，与巢蛋白增强子结合的转录因子还没有完全阐明。在这里，我们证明了鼠巢蛋白基因的第二个内含子足以在发育中的神经系统中驱动报告基因的表达。这种中枢神经系统特异性增强子的核心序列位于3‘320-bp区域。SOX和POU家族转录因子的顺式元件和激素反应元件在胚胎癌P19细胞神经分化过程中和发育中的鸡神经管中对Nestin的表达是必不可少的。有趣的是，在P19细胞神经分化和中枢神经系统发育的不同阶段，不同的转录因子与Nestin增强子结合。在未分化的P19EC细胞中，Sox2和SF1可能介导基础巢蛋白的表达，而在P19神经前体细胞中，Sox2、Brn1和Brn2与增强子结合。同样，在体内，Oct1在胚胎8.5天(E8.5)的小鼠胚胎中与巢蛋白增强子结合，而Oct1、Brn1和Brn2在E10.5和E12.5小鼠胚胎中与该增强子结合。因此，我们的研究表明，转录因子在决定Nestin基因表达时存在时间上的协调。
Nestin is a molecular marker for neural progenitor cells. Rat and human nestin genes possess a central nervous system-specific enhancer within their second introns. However, the transcription factors that bind to the nestin enhancer have not been fully elucidated. Here, we show that the second intron of the mouse nestin gene is sufficient to drive reporter gene expression in the developing nervous system. The core sequence of this central nervous system-specific enhancer localizes to the 3' 320-bp region. The cis-elements for Sox and POU family transcription factors and the hormone-responsive element are essential for nestin expression during embryonic carcinoma P19 cell neural differentiation and in the developing chick neural tube. Interestingly, different transcription factors bind to the nestin enhancer at different stages of P19 cell neural differentiation and central nervous system development. Sox2 and SF1 may mediate basal nestin expression in undifferentiated P19EC cells, whereas Sox2, Brn1, and Brn2 bind to the enhancer in P19 neural progenitor cells. Similarly, in vivo, Oct1 binds to the nestin enhancer in embryonic day 8.5 (E8.5) mouse embryos, and Oct1, Brn1, and Brn2 bind to this enhancer in E10.5 and E12.5 mouse embryos. Our studies therefore suggest a temporal coordination of transcription factors in determining nestin gene expression.