Regulation of the gene for human dipeptidyl peptidase IV by hepatocyte nuclear factor 1 alpha

Hepatocyte nuclear factor 1 was identified as the transcription factor bind ing to a 20 bp (-150 to -131) region of the gene for human dipeptidyl pepti dase IV, which has been shown to be important for the expression of dipepti dyl peptidase IV in the human intestinal and hepatic epithelial cell lines Caco-2 and HepG2. Functional analysis of the hepatocyte nuclear factor 1 si te was performed with two minimal dipeptidyl peptidase IV promoter construc ts (-250 to -41, and -150 to -41) with and without a 3 bp mutation in the h epatocyte nuclear factor 1 sequence, anal used in transient transfection ex periments with Caco-2 cells. The results show that the mutated constructs w ere able to drive transcription at only 5-10% of the activity of the non-mu tated controls. Co-transfection of 3T3 cells with hepatocyte nuclear factor 1 (alpha or beta) and dipeptidyl peptidase IV promoter constructs (-250 to -41 or -150 to -41) resulted in a 2.5-6-fold increase in transcription ove r controls with hepatocyte nuclear factor la but not with hepatocyte nuclea r factor 1 beta. The results of this study show that hepatocyte nuclear fac tor 1 binds to the -150 to -131 region of the human dipeptidyl peptidase IV promoter and is necessary for transcriptional activation of the gene for d ipeptidyl peptidase IV.