Hyperphosphorylation of MEF2A in primary adipocytes correlates with downregulation of human GLUT4 gene promoter activity.
GLUT4 promoter activity is regulated by hormonal, metabolic, and tissue-specific controls. This complicates the study of GLUT4 gene transcription, as no cell culture model adequately recapitulates these extracellular regulators. While investigating cultured primary adipocytes as a model system for GLUT4 transcription, we observed that GLUT4 mRNA was specifically and rapidly downregulated upon tissue dispersal. Downregulation of GLUT4 mRNA was mediated in part by loss of regulatory control by the trans-acting factors that control GLUT4 transcriptional activity [the myocyte enhancer factor 2 (MEF2) transcription factor family and the GLUT4 enhancer factor] and their cognate DNA binding sites in transgenic mice. The differences in GLUT4 transcription when whole adipose tissue and cell culture model systems are compared can be correlated to a posttranslational phosphorylation of the transcription factor MEF2A. The difference in the MEF2A phosphorylation state in whole tissue vs. isolated cells may provide a further basis for the development of an in vitro system that could recapitulate fully regulated GLUT4 promoter activity. Development of an in vitro system to reconstitute GLUT4 transcriptional regulation will further efforts to discern the molecular mechanisms that underlie GLUT4 expression.
Sparling
David P
DP
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, PO Box 26901, Rm. 853-BMSB, Oklahoma City, OK 73190, USA.
Griesel
Beth A
BA
Olson
Ann Louise
AL
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D015536:Down-Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014158:Transcription, Genetic
D051275:Glucose Transporter Type 4; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; C578044:Mef2d protein, mouse; D018006:Myogenic Regulatory Factors