Interaction between the homeodomain proteins Cdx2 and HNF1alpha mediates expression of the lactase-phlorizin hydrolase gene.

摘要: Lactase-phlorizin hydrolase is a brush-border enzyme which specifically expressed in the small intestine where it hydrolyses lactose, main carbohydrate found milk. We have previously demonstrated transgenic mice that tissue-specific and developmental expression of lactase controlled by 1 kb upstream region pig gene. Two homeodomain transcription factors, caudal-related protein (Cdx2) hepatic nuclear factor 1alpha (HNF1alpha), are known to bind regulatory cis elements promoters for several intestine-specific genes, including lactase, present mammalian intestinal epithelia from an early stage development. In study, we examined whether Cdx2 HNF1alpha physically interact co-operatively activate lactase-phlorizin promoter. show presence both factors leads much higher level than sum activation either alone. The N-terminal domain required maximal synergy with HNF1alpha. With use pull-down assays, demonstrate direct protein-protein interaction between includes proteins. This first demonstration functional two involved number genes. Synergistic tissue-restricted likely be important mechanism reinforcing gene within intestine.