Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the activation of the liver-specific protein C gene.
We have previously characterized the functional cis elements of the protein C promoter. One hepatocyte nuclear factor-1 (HNF-1) site, three HNF-3 sites, and at least two NF-I sites have been identified within the 140-bp basal transcriptional unit of this promoter. Here we present evidence that either HNF-1alpha or HNF-3 can cooperate with each other in binding to their cis elements. The results from the co-transfection assays in HeLa cells showed a novel synergistic transactivation between HNF-1alpha and HNF-3. Our data further indicate that the unique overlapping of the HNF-3 sites, the specific spatial relationship of the sites, and the co-activator C/EBP all contributed to the synergistic interaction. Although NF-I itself has a weak transactivating effect, it apparently coordinates the transactivation complex formation. NF-I can synergistically enhance the transactivation of HNF-1alpha or HNF-3. Taken together, the combinatorial interplay of HNF-1alpha, HNF-3, and NF-I make a significant contribution to the activation of the liver-specific protein C gene.
Tsay
W
W
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Republic of China.
Lee
Y M
YM
Lee
S C
SC
Shen
M C
MC
Chen
P J
PJ
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051541:Hepatocyte Nuclear Factor 3-alpha; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D051839:NFI Transcription Factors; D009687:Nuclear Proteins / Q000235:genetics*; D011486:Protein C / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation; D051840:Y-Box-Binding Protein 1
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C496501:Foxa1 protein, rat; D051538:Hepatocyte Nuclear Factor 1-alpha; D051541:Hepatocyte Nuclear Factor 3-alpha; C496489:Hnf1a protein, rat; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D011486:Protein C; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C486169:Ybx1 protein, rat; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta