A mechanism of differential expression of GLUT2 in hepatocyte and pancreatic beta-cell line.
- Author:
Jae Woo KIM
1
;
Yu Kyong KIM
;
Yong Ho AHN
Author Information
1. Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
GLUT2 gene expression;
hepatocyte;
beta-cell;
upstream promoter element
- MeSH:
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
- From:Experimental & Molecular Medicine
1998;30(1):15-20
- CountryRepublic of Korea
- Language:English
-
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.
