Transcriptional regulation of the human GLUT4 gene promoter in diabetic transgenic mice.
We previously reported that 2400 base pairs (bp) of 5'-flanking DNA is sufficient for tissue-specific and hormonal/metabolic regulation of the human GLUT4 gene in transgenic mice (Liu, M.-L., Olson, A. L., Moye-Rowley, W. S., Buse, J. B., Bell, G. I., and Pessin, J. E. (1992) J. Biol. Chem. 267, 11673-11676). To further define the DNA sequences required for GLUT4 expression, we generated transgenic mice carrying 1975, 1639, 1154, 730, and 412 bp of the GLUT4 5'-flank (hG4) fused to the chloramphenicol acetyltransferase (CAT) reporter gene. The 1975-hG4-CAT, 1639-hG4-CAT, and 1154-hG4-CAT constructs were expressed in a tissue-specific manner identical to the endogenous murine GLUT4 mRNA. Regulation of these reporter gene constructs in insulin-deficient diabetes also paralleled the endogenous gene. In contrast, 730-hG4-CAT was expressed at high levels only in skeletal muscle and at low levels in all of the other tissues examined. Additionally, expression of 412-hG4-CAT was completely unrestricted. Neither the 730-hG4-CAT nor the 412-hG4-CAT reporter genes displayed any insulin-dependent regulation. These data demonstrate that a skeletal muscle-specific DNA element is located within 730 bp of the GLUT4 5'-flanking DNA but that 1154 bp is necessary to direct the full extent of tissue-specific and insulin-dependent regulation of the human GLUT4 gene in transgenic mice.
Olson
A L
AL
Department of Physiology and Biophysics, University of Iowa, Iowa City 52242, USA.
Pessin
J E
JE
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics*; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution
D004274:DNA, Recombinant; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; D015500:Chloramphenicol O-Acetyltransferase