The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis.
The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; Nr2f2) is expressed in adipose tissue in vivo and declines during differentiation. Overexpression of COUP-TFII prevents adipogenesis, whereas shRNA-mediated reduction of COUP-TFII promotes differentiation, as shown by increased lipid accumulation and elevated expression of fat cell marker proteins. Furthermore, reduction of COUP-TFII allows uncommitted fibroblasts to be differentiated into fat cells. COUP-TFII represses the expression of a number of proadipogenic factors in adipocytes, with direct action noted at the CAAT enhancer-binding protein alpha promoter. We show that COUP-TFII acts downstream of hedgehog signaling and is required for the full antiadipogenic effect of this pathway. This effect is mediated in part by interaction with GATA factors. COUP-TFII and GATA2 are physically associated and repress target gene expression in an additive manner. Taken together, our data demonstrate that COUP-TFII represents an endogenous suppressor of adipogenesis, linking antiadipogenic extracellular signals to the core transcriptional cascade.
Xu
Zhao
Z
Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Yu
Songtao
S
Hsu
Chung-Hsin
CH
Eguchi
Jun
J
Rosen
Evan D
ED
D016475:3T3 Cells; D050156:Adipogenesis; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000378:metabolism*; D002645:Chickens; D050980:GATA Transcription Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism; D051379:Mice; D010047:Ovalbumin / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
D051837:COUP Transcription Factor II; D050980:GATA Transcription Factors; D053823:Hedgehog Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D010047:Ovalbumin