HNF Factors Form a Network to Regulate Liver-Enriched Genes in Zebrafish

Dev Biol. 2006 Jun 15;294(2):482-96. doi: 10.1016/j.ydbio.2006.03.018. Epub 2006 Apr 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Embryo, Nonmammalian / anatomy & histology
  • Embryo, Nonmammalian / physiology
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Hepatocyte Nuclear Factors / genetics
  • Hepatocyte Nuclear Factors / metabolism*
  • Humans
  • In Situ Hybridization
  • Liver / embryology
  • Liver / physiology*
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Promoter Regions, Genetic
  • Sequence Alignment
  • Zebrafish / anatomy & histology
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish / physiology
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • Hepatocyte Nuclear Factors
  • Oligonucleotides, Antisense
  • Zebrafish Proteins