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

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,...

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Bibliographic Details
Published in:Experimental & molecular medicine 1998-03, Vol.30 (1), p.15-20
Main Authors: Kim, J W, Kim, Y K, Ahn, Y H
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cell Line
Deoxyribonuclease I
DNA Footprinting
Gene Expression Regulation
Glucose Transporter Type 2
Islets of Langerhans - cytology
Islets of Langerhans - metabolism
Liver - cytology
Liver - metabolism
Monosaccharide Transport Proteins - biosynthesis
Monosaccharide Transport Proteins - genetics
Promoter Regions, Genetic
Protein Binding
Rats
Transcription Factor AP-1
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Summary: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.
ISSN:1226-3613
2092-6413
2092-6413
DOI:10.1038/emm.1998.2