Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by β-catenin in mice.

Pericentral activity of alpha-fetoprotein enhancer 3 and glutamine synthetase upstream enhancer in the adult liver are regulated by β-catenin in mice.
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DOI:
10.1002/hep.25819
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发表时间:
2012-11
期刊:
影响因子:
13.5
通讯作者:
Spear, Brett T.
Spear, Brett T.
中科院分区:
医学1区
文献类型:
--
作者:
Clinkenbeard, Erica L.;Butler, James E.;Spear, Brett T.

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We previously showed that mouse alpha-fetoprotein enhancer E3 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 TCF/LEF binding site that is required for responsiveness to β-catenin. We also show that endogenous AFP mRNA levels in the perinatal liver are lower when β-catenin is reduced. 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.
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