Peroxisome proliferator-activated receptor gamma and chicken ovalbumin upstream promoter transcription factor II negatively regulate the phosphoenolpyruvate carboxykinase promoter via a common element
Dw. Eubank et al., Peroxisome proliferator-activated receptor gamma and chicken ovalbumin upstream promoter transcription factor II negatively regulate the phosphoenolpyruvate carboxykinase promoter via a common element, J BIOL CHEM, 276(32), 2001, pp. 30561-30569
A heterodimer of peroxisome proliferator-activated receptor gamma (PPAR gam
ma) and retinoid X receptor (RXR) is required for adipocyte differentiation
. The gene encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is
a PPAR gamma /RXR target gene in adipose tissue. Of the two PPAR gamma resp
onse elements, gAF1/PCK1 and PCK2, only PCK2 is required for PEPCK expressi
on and responsiveness to the PPAR gamma agonist, rosiglitazone, in adipose
tissue even though both elements bind PPAR gamma /RXR in vitro. In contrast
, gAF1/PCK1 is essential for glucocorticoid inhibition of PPAR gamma -induc
ed PEPCK gene expression in adipocytes. We report that chicken ovalbumin up
stream promoter transcription factor II (COUP-TFII) is the predominant nucl
ear receptor bound to gAF1/PCK1 in preadipocytes. COUP-TFII declines during
adipogenesis in reciprocal fashion to PPAR gamma. In transiently transfect
ed fibroblasts COUP-TFII acts at gAF1/PCK1 to inhibit PPAR gamma /RXR activ
ation via PCK2. In contrast COUP-TFs are transcriptional activators of PEPC
K in hepatocytes. PPAR gamma /RXR occupies gAF1/PCK1 in adipocytes, and mut
ation of gAF1/PCK1 enhances PEPCK promoter transactivation by PPAR gamma /R
XR in fibroblasts, suggesting that this element is also a negative PPAR gam
ma response element. These results indicate that gAF1/PCK1 is a pleiotropic
element through which COUP-TFII inhibits premature PEPCK expression, and p
erhaps adipogenesis in general, and PPAR gamma /RXR uses this same element
in adipocytes to participate in PEPCK modulation by glucocorticoids.