Exp Mol Med.  1998 Mar;30(1):15-20.

A mechanism of differential expression of GLUT2 in hepatocyte and pancreatic beta-cell line

• Kim JW
• Kim YK
• Ahn YH

Abstract

DNase I footprinting assay using liver nuclear extracts revealed six protected regions between nucleotide -600 and +110 and hence named Box I-VI. Upstream promoter element (UPE), a DNA element playing crucial role in transcriptional control of the tissue specific expression of pancreatic beta-cell, has been detected within the proximal region of rat GLUT2 promoter. This region is included in Box VI. The protein-DNA interaction in this region (Box VI) was confirmed by mobility shift assay using liver nuclear extracts. Deletion of the region between -585 bp and -146 bp resulted in dramatic changes in promoter activity when they were expressed in liver and beta-cell derived cell line. When -585/-146 construct was expressed in liver, the activity was decreased to 46%, whereas the activity in beta-cell line, HIT-T15 cell, was increased by 84% when compared to -146/+190 construct. These opposing phenomena can be explained by the fact that beta-cell specifically expresses the UPE binding protein. Assuming that there may be Box VI-binding protein playing negative roles both in hepatocyte and beta-cell, and that the protein acts as a negative regulator of GLUT2 gene, the UPE binding protein in the beta-cell may overcome the inhibition by binding to the protein.

Keyword

GLUT2 gene expression; hepatocyte; beta-cell; upstream promoter element

MeSH Terms

Animal
Binding Sites
Cell Line
Comparative Study
DNA Footprinting
Deoxyribonuclease I
Gene Expression Regulation
Islets of Langerhans/metabolism*
Islets of Langerhans/cytology
Liver/metabolism*
Liver/cytology
Monosaccharide Transport Proteins/genetics
Monosaccharide Transport Proteins/biosynthesis*
Promoter Regions (Genetics)*
Protein Binding
Rats
Transcription Factor AP-1