Downregulation of repressive CUP/AP-2 isoforms during adipocyte differentiation.
Activation of transcription of the C/EBPalpha (CCAAT/enhancer binding protein alpha) gene is a critical event in the differentiation of 3T3-L1 preadipocytes into adipocytes. The kinetics of this process parallels a decline of AP-2alpha protein (also referred to as CUP, C/EBP undifferentiated protein) and decreased binding of CUP/AP-2alpha to the C/EBPalpha promoter. Mutation of the CUP/AP-2 binding sites in the C/EBPalpha promoter results in increased C/EBPalpha expression. Based on these findings, it appears that decline in AP-2alpha expression is an important early event in the adipocyte differentiation program. In the studies presented here, we identify three mRNAs that encode the repressive CUP/AP-2alpha isoforms expressed in undifferentiated 3T3-L1 preadipocytes. We demonstrate that the kinetics of the decline of these isoforms' expression over the course of differentiation parallels both the decrease in CUP/AP-2alpha DNA binding activity and the increase in C/EBPalpha protein observed in previous studies.
Holt
E H
EH
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Lane
M D
MD
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D015536:Down-Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D023282:Nuclease Protection Assays; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics*; D020218:Response Elements / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D004268:DNA-Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012097:Repressor Proteins; C493668:Tfap2a protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors