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

Abstract

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 γ (PPARγ) 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 α (C/EBPα) and C/EBPβ, members of a family of transcription factors that are integral to adipogenesis. We mapped this interaction to the basic leucine zipper domain of C/EBPα 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 PPARγ transcriptional activity, interaction of GATA factors with C/EBP is necessary for their ability to negatively regulate adipogenesis.

ACKNOWLEDGMENTS

This work was supported by National Research Service Association (NRSA) grant F32 DK09940 and a National Institutes of Health (NIH) postdoctoral training fellowship (Q.T.), National Institute of Environmental Health Sciences (NIEHS) training grant EK56894 (J.T.), and NIH grant DK56894 (G.S.H.).