Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta regulate transcription via two elements in an intestine-specific promoter

Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta are transcription factors that contain a divergent homeodomain, bind to DNA as homo- or heterodimers, and act to regulate transcription of many genes that are expressed primarily in liver. We show that HNF-1 alpha and HNF-1 beta act as regulatory factors for transcription of sucrase-isomaltase (SI), the gene for which is expressed exclusively in absorptive enterocytes of the small intestine. HNF-1 alpha and HNF-1 beta bind to two evolutionarily conserved sites in the SI promoter, previously named SIF2 and SIF3, with different relative affinities. HNF-1 alpha binds to the SIF3 element with greater affinity than to the SIF2 element, whereas HNF-1 beta binds to both elements equally. Co-transfection experiments demonstrated that HNF-1 alpha is able to increase transcriptional initiation from a minimal SI intestine-specific promoter. In contrast, HNF-1 beta has no functional effect on transcription of the SI promoter. The functional and DNA binding differences of HNF-1 alpha and HNF-1 beta on elements in the SI promoter suggest that these transcription factors may play a role in the complex spatial patterns of SI gene expression in the intestine.