Sequential gene promoter interactions by C/EBPbeta, C/EBPalpha, and PPARgamma during adipogenesis.
Treatment of 3T3-L1 preadipocytes with differentiation inducers triggers a cascade in which C/EBPbeta is rapidly expressed, followed by C/EBPalpha and PPARgamma. C/EBPalpha and PPARgamma then activate the expression of adipocyte genes that produce the differentiated phenotype. Circumstantial evidence indicates that C/EBPbeta activates transcription of the C/EBPalpha and PPARgamma genes, both of which possess C/EBP regulatory elements in their proximal promoters. Although C/EBPbeta is expressed immediately upon induction of differentiation, acquisition of DNA binding activity is delayed for approximately 14h. Chromatin immunoprecipitation (ChIP) analysis conducted 24h after induction revealed that C/EBPbeta binds to C/EBP regulatory elements in the proximal promoters of the C/EBPalpha and PPARgamma genes. ChIP analysis showed that after an additional delay C/EBPalpha binds to its own promoter and to the promoters of the PPARgamma and 422/aP2 genes. These findings support the view that once expressed, C/EBPalpha is responsible for maintaining the expression of PPARgamma, and C/EBPalpha, as well as adipocyte proteins (e.g., 422/aP2) in the terminally differentiated state. Together these findings provide compelling evidence that C/EBPbeta, C/EBPalpha, and PPARgamma participate in a cascade during adipogenesis.
Tang
Qi-Qun
QQ
Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe Street Baltimore, MD 21205, USA.
Zhang
Jiang-Wen
JW
Daniel Lane
M
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D002843:Chromatin; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D004247:DNA