期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2000
卷号:97
期号:23
页码:12519-12523
DOI:10.1073/pnas.220426097
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:CCAAT enhancer-binding protein- (C/EBP) functions as a pleiotropic transcriptional activator of adipocyte genes during adipogenesis. Nuclear factor C/EBP undifferentiated protein (CUP), an isoform of activator protein-2 (AP-2), binds to repressive elements in the C/EBP gene promoter, silencing the gene until late in the differentiation program. The CUP regulatory element overlaps a Sp (GT-box) element in the promoter to which Sp3 (or Sp1) can bind. Binding by Sp3 or Sp1 and CUP/AP2- is mutually exclusive. Sp3 is a strong transcriptional activator of the C/EBP gene promoter in 3T3-L1 preadipocytes and Schneider cells, this activation being repressed by CUP/AP-2. Sp3 is expressed throughout differentiation, whereas CUP/AP-2, which is expressed only by preadipocytes, is down-regulated during differentiation coincident with transcription of the C/EBP gene. Thus, CUP/AP-2 delays access of Sp3 to the Sp regulatory element, preventing premature expression of C/EBP and thereby interference by C/EBP (which is antimitotic) with mitotic clonal expansion, an essential early event in the differentiation program.