Sucrase-isomaltase gene transcription requires the hepatocyte nuclear factor-1 (HNF-1) regulatory element and is regulated by the ratio of HNF-1 alpha to HNF-1 beta.
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-1 alpha complex with a concomitant decrease in the HNF-1 beta-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-1 alpha activated the SI promoter via the SIF3 element, and co-expression of HNF-1 beta 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-1 alpha to HNF-1 beta plays a role in the transcriptional activity of this gene during intestinal development.
Boudreau
F
F
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhu
Y
Y
Traber
P G
PG
D000818:Animals; D001483:Base Sequence; D018938:Caco-2 Cells; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000254:growth & development; D051379:Mice; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D013394:Sucrase-Isomaltase Complex / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D017931:DNA Primers; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C496496:Hnf1b protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D013394:Sucrase-Isomaltase Complex