Sucrase-isomaltase Gene Transcription Requires the Hepatocyte Nuclear Factor-1 (HNF-1) Regulatory Element and Is Regulated by the Ratio of HNF-1α to HNF-1β*

By F. Boudreau, Yi Zhu, P. Traber. Journal of Biological Chemistry, 2001

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The mouse sucrase-isomaltase (SI) gene is an enterocyte-specific gene expressed in a complex developmental pattern. We previously reported that a short, evolutionarily conserved gene promoter regulates developmental expression of SI in mouse small intestine. Herein, we investigated the role of a hepatocyte nuclear factor-1 (HNF-1) cis-acting element to regulate SI gene expression in vivo. Transgenic SI gene constructs with a mutated HNF-1 element (SIF3) revealed a strong reduction in promoter activity in comparison with a wild-type construct in mice and during Caco-2 cell differentiation. Nuclear proteins isolated from enterocytes showed increased binding of the HNF-1α complex with a concomitant decrease in the HNF-1β-containing complex to the SIF3 element both during the suckling-weaning developmental transition and Caco-2 cell differentiation. These changes coincided with a strong induction of SI gene transcription. In transfection experiments, HNF-1α activated the SI promoter via the SIF3 element, and co-expression of HNF-1β impaired this transcriptional activation. These findings demonstrate the essential role of the HNF-1 regulatory element to support SI gene transcription in vivo and suggest that the ratio of HNF-1α to HNF-1β plays a role in the transcriptional activity of this gene during intestinal development.

Subfields: Genetics

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