GATA proteins work together with friend of GATA (FOG) and C-terminal binding protein (CTBP) co-regulators to control adipogenesis

J Biol Chem. 2010 Oct 15;285(42):32405-14. doi: 10.1074/jbc.M110.141317. Epub 2010 Aug 11.

Abstract

GATA transcription factors have been implicated in controlling adipogenesis in Drosophila and in mammals. In mammals, both GATA2 and GATA3 have been shown to be present in preadipocytes, and their silencing allows the onset of adipogenesis. Overexpression of GATA proteins blocks adipogenesis in cellular assays. GATA factors have been found to operate through recruiting cofactors of the Friend of GATA (FOG) family. FOG proteins, in turn, recruit co-regulators, including C-terminal binding proteins (CTBPs). We have investigated whether FOGs and CTBPs influence adipogenesis. We found that both FOG1 and FOG2 are expressed in cells prior to adipogenesis but are down-regulated as adipogenesis proceeds. Overexpression of FOG1 or FOG2 interferes with adipogenesis. Mutant versions of FOG2 unable to bind CTBP or GATA proteins are impaired in their inability to inhibit adipogenesis. Finally, a mutant version of GATA2, unable to associate with FOGs, also displays abnormal activity and causes enhanced cell proliferation. These results implicate FOGs and CTBPs as partners of GATA proteins in the control of adipocyte proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / physiology*
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism*
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GATA Transcription Factors / genetics
  • GATA Transcription Factors / metabolism*
  • Humans
  • Male
  • Mice
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA, Small Interfering / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • GATA Transcription Factors
  • Nuclear Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • ZFPM2 protein, human
  • Zfpm1 protein, mouse
  • Alcohol Oxidoreductases
  • C-terminal binding protein