Potential conflict of interest: Nothing to report.
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Liver Biology/Pathobiology
Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by β-catenin in mice†‡
Article first published online: 31 OCT 2012
DOI: 10.1002/hep.25819
Copyright © 2012 American Association for the Study of Liver Diseases
Additional Information
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
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Potential conflict of interest: Nothing to report.
- ‡
These authors contributed equally to this work.
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Publication History
- 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
Funded by
- Public Health Service. Grant Number: DK-074816
- Abstract
- Article
- References
- Cited By
Abstract
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)