Tandem repeat of C/EBP binding sites mediates PPARγ2 gene transcription in glucocorticoid-induced adipocyte differentiation

Shi Xing Ming, Harry C. Blair, Xiangli Yang, Jay M. McDonald, Cao Xu

Research output: Contribution to journalArticle

Abstract

Bone marrow stromal stem cells differentiate into many different types of cells including osteoblasts and adipocytes. Long-term glucocorticoid treatment decreases osteoblastic activity but increases adipocytes. We investigated the mechanism of glucocorticoid-induced PPARγ2 transcription. Treatment of human bone marrow stromal cells with dexamethasone induced the differentiation of these cells into adipocytes as measured by oil-red O staining, and Northern blot analysis showed that dexamethasone strongly induced PPARγ2 mRNA expression in cells cultured in adipocyte induction medium. Moreover, the mRNA of C/EBPδ, an adipocyte-promoting transcription factor, was also induced by dexamethasone in the presence of induction medium. Gel mobility shift assays using purified GST-C/EBPδ fusion protein showed that C/EBPδ specifically binds to a 40-base pair DNA element from PPARγ2 promoter, which was found to contain a tandem repeat of C/EBP binding sites. Transfection studies in mouse mesenchymal C3H10T1/2 cells showed that it is the tandem repeat of the C/EBP binding site in PPARγ2 promoter region that regulates dexamethasone-mediated PPARγ2 gene activation. We conclude that glucocorticoid-induced adipogenesis from bone marrow stromal cells is mediated through a reaction cascade in which dexamethasone transcriptionally activates C/EBPδ; C/EBPδ then binds to PPARγ2 promoter and transactivates PPARγ2 gene expression. This activated master regulator, in turn, initiates the adipocyte differentiation.

Original languageEnglish (US)
Pages (from-to)518-527
Number of pages10
JournalJournal of cellular biochemistry
Volume76
Issue number3
DOIs
StatePublished - Feb 14 2000
Externally publishedYes

Keywords

  • Adipocyte
  • Bone marrow stromal cell
  • Glucocorticoid
  • Osteoblast
  • Osteoporosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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