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.
Brodie
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AE
Department of Animal Sciences, Oregon State University, Corvallis 97331-6702, USA.
Manning
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VA
Hu
C Y
CY
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D051838:COUP Transcription Factor I; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497590:Nr2f1 protein, mouse; D000072317:Polychlorinated Dibenzodioxins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin