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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0033684,
umls-concept:C0035143,
umls-concept:C0086860,
umls-concept:C0108685,
umls-concept:C0185117,
umls-concept:C0330390,
umls-concept:C0596843,
umls-concept:C0752063,
umls-concept:C1333891,
umls-concept:C1537647,
umls-concept:C1546857,
umls-concept:C1879547,
umls-concept:C2003941,
umls-concept:C2911684
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pubmed:issue |
12
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pubmed:dateCreated |
2006-3-20
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pubmed:abstractText |
Studies have shown that CCAAT/enhancer-binding protein beta (C/EBP beta) can stimulate adipogenesis in noncommitted fibroblasts by activating expression of peroxisome proliferator-activated receptor-gamma (PPARgamma). Other investigations have established a role for C/EBP alpha as well as PPARgamma in orchestrating the complex program of adipogenic gene expression during terminal preadipocyte differentiation. Consequently, it is important to identify factors regulating transcription of the C/ebp alpha gene. In this study, we demonstrated that inhibition of PPARgamma activity by exposure of 3T3-L1 preadipocytes to a potent and selective PPARgamma antagonist inhibits adipogenesis but also blocks the activation of C/EBP alpha expression at the onset of differentiation. Ectopic expression of C/EBP beta in Swiss 3T3 mouse fibroblasts (Swiss-LAP cells) induces PPARgamma expression without any significant enhancement of C/EBP alpha expression. Treatment of Swiss-LAP cells with a PPARgamma agonist induces adipogenesis, which includes activation of C/EBP alpha expression. To further establish a role for PPARgamma in regulating C/EBP alpha expression, we expressed C/EBP beta in PPARgamma-deficient mouse embryo fibroblasts (MEFs). The data show that C/EBP beta is capable of inducing PPARgamma in Ppar gamma+/- MEFs, which leads to activation of adipogenesis, including C/EBP alpha expression following exposure to a PPARgamma ligand. In contrast, C/EBP beta is not able to induce C/EBP alpha expression or adipogenesis in Ppar gamma-/- MEFs. Chromatin immunoprecipitation analysis reveals that C/EBP beta is bound to the minimal promoter of the C/ebp alpha gene in association with HDAC1 in unstimulated Swiss-LAP cells. Exposure of the cells to a PPARgamma ligand dislodges HDAC1 from the proximal promoter of the C/ebp alpha gene, which involves degradation of HDAC1 in the 26 S proteasome. These data suggest that C/EBP beta activates a single unified pathway of adipogenesis involving its stimulation of PPARgamma expression, which then activates C/EBP alpha expression by dislodging HDAC1 from the promoter for degradation in the proteasome.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP dependent 26S protease,
http://linkedlifedata.com/resource/pubmed/chemical/Azo Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Benzamides,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-beta,
http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/T 0070907,
http://linkedlifedata.com/resource/pubmed/chemical/oil red O
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7960-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16431920-3T3-L1 Cells,
pubmed-meshheading:16431920-Adipocytes,
pubmed-meshheading:16431920-Animals,
pubmed-meshheading:16431920-Azo Compounds,
pubmed-meshheading:16431920-Benzamides,
pubmed-meshheading:16431920-Blotting, Western,
pubmed-meshheading:16431920-CCAAT-Enhancer-Binding Protein-alpha,
pubmed-meshheading:16431920-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:16431920-Cell Differentiation,
pubmed-meshheading:16431920-Cells, Cultured,
pubmed-meshheading:16431920-Chromatin Immunoprecipitation,
pubmed-meshheading:16431920-Fibroblasts,
pubmed-meshheading:16431920-Gene Expression Regulation,
pubmed-meshheading:16431920-Histone Deacetylase 1,
pubmed-meshheading:16431920-Histone Deacetylases,
pubmed-meshheading:16431920-Immunoprecipitation,
pubmed-meshheading:16431920-Ligands,
pubmed-meshheading:16431920-Lipid Metabolism,
pubmed-meshheading:16431920-Lipids,
pubmed-meshheading:16431920-Mice,
pubmed-meshheading:16431920-PPAR gamma,
pubmed-meshheading:16431920-Promoter Regions, Genetic,
pubmed-meshheading:16431920-Proteasome Endopeptidase Complex,
pubmed-meshheading:16431920-Pyridines,
pubmed-meshheading:16431920-RNA,
pubmed-meshheading:16431920-Transcription, Genetic
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pubmed:year |
2006
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pubmed:articleTitle |
Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta during adipogenesis requires a peroxisome proliferator-activated receptor-gamma-associated repression of HDAC1 at the C/ebp alpha gene promoter.
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pubmed:affiliation |
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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