The orphan nuclear receptor chicken ovalbumin upstream promoter- transcription factor II is a critical regulator of adipogenesis

Zhao Xu, Songtao Yu, Chung Hsin Hsu, Jun Eguchi, Evan D. Rosen

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

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 α 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.

Original languageEnglish
Pages (from-to)2421-2426
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number7
DOIs
Publication statusPublished - Feb 19 2008
Externally publishedYes

Keywords

  • Differentiation
  • GATA
  • Nr2f2
  • Repressor

ASJC Scopus subject areas

  • General

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