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PMID: 11050170 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Sequential repression and activation of the CCAAT enhancer-binding protein-alpha (C/EBPalpha ) gene during adipogenesis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 23 ·2000-11-07 ·Pages 12519-23

Jiang MS, Lane MD

Abstract

CCAAT enhancer-binding protein-alpha (C/EBPalpha) functions as a pleiotropic transcriptional activator of adipocyte genes during adipogenesis. Nuclear factor C/EBP undifferentiated protein (CUP), an isoform of activator protein-2alpha (AP-2alpha), binds to repressive elements in the C/EBPalpha 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-alpha is mutually exclusive. Sp3 is a strong transcriptional activator of the C/EBPalpha gene promoter in 3T3-L1 preadipocytes and Schneider cells, this activation being repressed by CUP/AP-2alpha. Sp3 is expressed throughout differentiation, whereas CUP/AP-2alpha, which is expressed only by preadipocytes, is down-regulated during differentiation coincident with transcription of the C/EBPalpha gene. Thus, CUP/AP-2alpha delays access of Sp3 to the Sp regulatory element, preventing premature expression of C/EBPalpha and thereby interference by C/EBPalpha (which is antimitotic) with mitotic clonal expansion, an essential early event in the differentiation program.

MeSH Terms
3T3 Cells Adipocytes Animals Binding Sites CCAAT-Enhancer-Binding Protein-alpha/genetics Cell Differentiation Cell Line DNA-Binding Proteins/genetics,metabolism Drosophila Proteins Drosophila melanogaster Electrophoresis, Polyacrylamide Gel/methods Gene Expression Regulation Genes, Overlapping Humans Kinetics Mice Nuclear Proteins/genetics,metabolism Oligonucleotides Promoter Regions, Genetic Sp1 Transcription Factor/metabolism Sp3 Transcription Factor Transcription Factor AP-2 Transcription Factors/genetics,metabolism Transcriptional Activation
Chemicals
CCAAT-Enhancer-Binding Protein-alpha CUP protein, human DNA-Binding Proteins Drosophila Proteins Nuclear Proteins Oligonucleotides SP3 protein, human Sp1 Transcription Factor Sp3 protein, mouse TFAP2A protein, human TfAP-2 protein, Drosophila Tfap2a protein, mouse Transcription Factor AP-2 Transcription Factors Sp3 Transcription Factor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Jiang M S
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Lane M D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.220426097
Published
2000-11-07
Pages
12519-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC18796
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.220426097 PMC Full Text View journal details
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