Sequential gene promoter interactions of 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. After an additional delay ChIP analysis showed that 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. qtang@jhem.jhmi.edu
Zhang
Jiang-Wen
JW
Daniel Lane
M
M
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D002454:Cell Differentiation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D015151:Immunoblotting; D051379:Mice; D010641:Phenotype; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D002843:Chromatin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004247:DNA