Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated suppression of adipocyte differentiation.
We have previously demonstrated that GATA-2 and GATA-3 are expressed in adipocyte precursors and control the preadipocyte-to-adipocyte transition. Constitutive expression of both GATA-2 and GATA-3 suppressed adipocyte differentiation, partially through direct binding to the peroxisome proliferator-activated receptor gamma (PPARgamma) promoter and suppression of its basal activity. In the present study, we demonstrate that both GATA-2 and GATA-3 form protein complexes with CCAAT/enhancer binding protein alpha (C/EBPalpha) and C/EBPbeta, members of a family of transcription factors that are integral to adipogenesis. We mapped this interaction to the basic leucine zipper domain of C/EBPalpha and a region adjacent to the carboxyl zinc finger of GATA-2. The interaction between GATA and C/EBP factors is critical for the ability of GATA to suppress adipocyte differentiation. Thus, these results show that in addition to its previously recognized function in suppressing PPARgamma transcriptional activity, interaction of GATA factors with C/EBP is necessary for their ability to negatively regulate adipogenesis.
Tong
Qiang
Q
Department of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Ave., Bldg. 1, Rm. 207, Boston, MA 02115, USA.
Tsai
Judy
J
Tan
Guo
G
Dalgin
Gökhan
G
Hotamisligil
Gökhan S
GS
D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D046912:Multiprotein Complexes; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494712:Gata2 protein, mouse; C494713:Gata2 protein, rat; C494748:Gata3 protein, mouse; D046912:Multiprotein Complexes; D047495:PPAR gamma; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA