Synergistic transactivation of HNF-1alpha, HNF-3, and NF-I contributes to the activation of the liver-specific protein C gene

DNA and Cell Biology
W TsayP J Chen

Abstract

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.

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Citations

Apr 13, 2000·Biochimica Et Biophysica Acta·M P PiechockiR J Ruch
Aug 3, 1999·Matrix Biology : Journal of the International Society for Matrix Biology·A Degterev, J A Foster
Jan 24, 2007·Physiological Reviews·Yutaka MaedaJeffrey A Whitsett
May 10, 2002·The Journal of Biological Chemistry·Michael B BoffaMarlys L Koschinsky
Mar 9, 2006·Clinical and Vaccine Immunology : CVI·David T BergBrian W Grinnell
Mar 21, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Joyce K DivineTheodore C Simon

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