Potential conflict of interest: Nothing to report.
Article first published online: 31 OCT 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 56, Issue 5, pages 1892–1901, November 2012
How to Cite
Clinkenbeard, E. L., Butler, J. E. and Spear, B. T. (2012), Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by β-catenin in mice. Hepatology, 56: 1892–1901. doi: 10.1002/hep.25819
These authors contributed equally to this work.
- Issue published online: 31 OCT 2012
- Article first published online: 31 OCT 2012
- Accepted manuscript online: 27 APR 2012 10:32AM EST
- Manuscript Accepted: 24 APR 2012
- Manuscript Received: 14 JAN 2012
- Public Health Service. Grant Number: DK-074816
We previously showed that mouse alpha-fetoprotein (AFP) enhancer 3 activity is highly restricted to pericentral hepatocytes in the adult liver. Here, using transgenic mice, we show that the upstream enhancer of the rat glutamine synthetase gene is also active, specifically in pericentral regions. Activity of both enhancers is lost in the absence of β-catenin, a key regulator of zonal gene expression in the adult liver. Both enhancers contain a single, highly conserved T-cell factor/lymphoid enhancer factor binding site that is required for responsiveness to β-catenin. We also show that endogenous AFP messenger RNA levels in the perinatal liver are lower when β-catenin is reduced. Conclusion: These data identify the first distinct zonally active regulatory regions required for β-catenin responsiveness in the adult liver, and suggest that postnatal AFP repression and the establishment of zonal regulation are controlled, at least in part, by the same factors. (HEPATOLOGY 2012;56:1892–1901)