HNF factors form a network to regulate liver-enriched genes in zebrafish
HNF factors form a network to regulate liver-enriched genes in zebrafish
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DOI：
10.1016/j.ydbio.2006.03.018
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发表时间：
2006-06-15
影响因子：
2.7
通讯作者：
Peng, Jinrong
中科院分区：
文献类型：
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作者：
Cheng, Wei;Guo, Lin;Peng, Jinrong
哺乳动物中某些肝脏富集基因的缺陷会导致肝脏和/或血液相关疾病。然而，由于哺乳动物胚胎发生在子宫内，这些肝脏富集基因在肝脏器官发生过程中的功能研究很少。我们在这里报告的129个真正的肝脏丰富的基因在成年斑马鱼的鉴定和显示，通过原位杂交，这些基因中的69个也丰富的胚胎肝脏。外部胚胎发生加上完善的吗啉介导的基因敲低技术在斑马鱼为我们提供了一个独特的机会，研究这组基因在肝脏器官发生过程中发挥任何作用，在未来。例如，使用吗啉代介导的基因敲除方法的初步研究显示，一个新的肝脏富集基因leg 1对肝脏扩张生长至关重要。我们还报告了通过寻找肝脏中富集的四种关键转录因子Hnf 1、Hnf 3、Hnf 4和Hnf 6的推定结合位点来分析51个肝脏富集基因的启动子区域。我们发现大多数肝脏富集基因的启动子区含有多个HNF因子的结合位点，这表明大多数肝脏富集基因可能受到不同HNF因子组合的共同调控。这一观察结果支持了这四种肝脏富集的转录因子在控制肝脏特异性或肝脏富集基因的表达中形成网络的假设。(c)2006年爱思唯尔公司All rights reserved.
Defects in some of liver-enriched genes in mammals will cause liver- and/or blood-related diseases. However, due to the fact that embryogenesis happens intrauterinally in the mammals, the function of these liver-enriched genes during liver organogenesis is poorly studied. We report here the identification of 129 genuine liver-enriched genes in adult zebrafish and show that, through in situ hybridization, 69 of these genes are also enriched in the embryonic liver. External embryogenesis coupled with the well-established morpholino-mediated gene knock-down technique in zebrafish offers us a unique opportunity to study if this group of genes plays any role during liver organogenesis in the future. As an example, preliminary study using morpholino-mediated gene knock-down method revealed that a novel liver-enriched gene leg1 is crucial for the liver expansion growth. We also report the analysis of promoter regions of 51 liver-enriched genes by searching putative binding sites for Hnf1, Hnf3, Hnf4 and Hnf6, four key transcription factors enriched in the liver. We found that promoter regions of majority of liver-enriched genes contain putative binding sites for more than one HNF factors, suggesting that most of liver-enriched genes are likely co-regulated by different combination of HNF factors. This observation supports the hypothesis that these four liver-enriched transcription factors form a network in controlling the expression of liver-specific or -enriched genes in the liver. (c) 2006 Elsevier Inc. All rights reserved.