Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor
Developmental regulation of galactokinase in suckling mouse liver by the Egr-1 transcription factor
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DOI：
10.1203/01.pdr.0000120682.05408.79
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发表时间：
2004-05-01
影响因子：
3.6
通讯作者：
Levitsky, LL
中科院分区：
文献类型：
--
作者：
Yang, F;Agulian, T;Levitsky, LL
伴随肝脏发育的代谢途径的许多变化引起基因表达的相关变化。Egr-1是一种锌指转录因子，在许多细胞类型中调节参与细胞生长、分化、应激反应和凋亡的基因。在啮齿类动物中，Egr-1在肝再生中被诱导，但其在正常肝细胞功能中的作用尚未被表征。我们研究了Egr-1在小鼠肝脏中的发育表达，发现其表达在哺乳期增加。在筛选参与乳糖同化的基因序列时，我们发现半乳糖激酶基因Glk在其近端启动子中含有四个潜在的Egr-1结合位点。一个最小的155个核苷酸的启动子，包括四个Egr-1网站表现出活性的肝癌细胞系通过瞬时转染试验。此外，Egr-1表达质粒的共转染增加了启动子活性。最后，引入到四个Egr-1结合位点中的三个中的突变降低了活性，而其余位点的突变增加了启动子活性。这些数据将Egr-1和半乳糖激酶结合在一起，形成一条发育调节链，为新生儿哺乳做好准备。
The numerous changes in metabolic pathways that accompany liver development entail associated changes in gene expression. Egr-1 is a zinc-finger transcription factor that regulates genes involved in cellular growth, differentiation, stress response, and apoptosis in many cell types. Egr-1 is induced in liver regeneration in rodents, but its role in normal hepatocyte function has not been characterized. We examined the developmental expression of Egr-1 in mouse liver and found that its expression increased during the suckling period. In screening the sequences of the genes involved in lactose assimilation, we found that the galactokinase gene Glk contains four potential Egr-1 binding sites in its proximal promoter. A minimal promoter of 155 nucleotides encompassing the four Egr-1 sites exhibited activity in hepatoma cell lines by transient transfection assays. Moreover, co-transfection of an Egr-1 expression plasmid increased promoter activity. Finally, mutations introduced into three of the four Egr-1 binding sites decreased activity, whereas mutation of the remaining site increased promoter activity. These data tie Egr-1 and galactokinase together in a developmentally regulated chain to prepare the neonate for suckling.