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CAAT/enhancer binding proteins directly modulate transcription from the peroxisome proliferator-activated receptor
S L Clarke1, C E Robinson, J M Gimble
1Immunobiology & Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Abstract:
The CCAAT/enhancer binding proteins (C/EBPs) and the peroxisome proliferator-activated receptors (PPARs) together regulate adipogenesis. The current work uses co-transfection studies to examine the C/ EBP dependence of PPAR gamma 2 transcription. Both C/ EBP alpha and C/EBP delta expression vectors activated transcription from a PPAR gamma 2 promoter/luciferase expression vector by 5-6 fold in UMR106 cells. The simultaneous transfection of the C/EBP homologous protein (CHOP) (also known as growth arrest DNA damage protein 153 or gadd153) inhibited this C/EBP-dependent activation in a concentration dependent manner. The CHOP protein is known to heterodimerize with other C/EBP proteins to form transcriptionally inactive complexes. Mutation of the two C/EBP DNA recognition elements at -340 bp and -327 bp within the PPAR gamma 2 promoter reduced the inductive effects of both C/EBP alpha and C/EBP delta. These findings demonstrate that proteins within the C/EBP family directly modulate transcription from the PPAR gamma 2 promoter.