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Molecular and Cellular Biology, January 2005, p. 706-715, Vol. 25, No. 2
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.2.706-715.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interaction between GATA and the C/EBP Family of Transcription Factors Is Critical in GATA-Mediated Suppression of Adipocyte Differentiation

Qiang Tong ,{dagger},{ddagger} Judy Tsai,{dagger} Guo Tan, Gökhan Dalgin, and Gökhan S. Hotamisligil*

Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts

Received 17 May 2004/ Returned for modification 2 August 2004/ Accepted 1 October 2004

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} (PPAR{gamma}) 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/EBP{alpha}) and C/EBPß, members of a family of transcription factors that are integral to adipogenesis. We mapped this interaction to the basic leucine zipper domain of C/EBP{alpha} 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 PPAR{gamma} transcriptional activity, interaction of GATA factors with C/EBP is necessary for their ability to negatively regulate adipogenesis.

* Corresponding author. Mailing address: Department of Genetics and Complex Diseases, 665 Huntington Ave., Bldg. 1, Rm. 207, Boston, MA 02115. Phone: (617) 432-1950. Fax: (617) 432-1941. E-mail: ghotamis{at}hsph.harvard.edu.

{dagger} Q.T. and J.T. contributed equally to this work.

{ddagger} Present address: Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX 77030.

Molecular and Cellular Biology, January 2005, p. 706-715, Vol. 25, No. 2
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.2.706-715.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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