Inhibitors of preadipocyte differentiation induce COUP-TF binding to a PPAR/RXR binding sequence.

Inhibition of preadipocyte differentiation by 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) or retinoic acid (RA) identified another transcription factor which appears to be important for preadipocyte differentiation. Within 15 min of treating 3T3-L1 cells with TCDD, the aryl hydrocarbon receptor (AhR) is present within the cell nucleus, and increased binding of COUP-TF to an oligomer of the PPAR gamma 2/RXR binding sequence (ARE7) occurs. Following 2 days of RA treatment, increased binding of COUP-TF to the ARE7 oligomer also occurs. In untreated preadipocytes, COUP-TF mRNA increased at confluence and then decreased after induction. TCDD treatment did not alter COUP-TF mRNA changes. Dephosphorylating the nuclear extracts from TCDD and RA-treated cells eliminated binding of COUP-TF to ARE7. This is the first indication that COUP-TF may play a role in preadipocyte differentiation and that COUP-TF binding to DNA is correlated with TCDD and RA-induced phosphorylation.