|Tsai, Judy - HARVARD SPH|
|Tan, Guo - HARVARD SPH|
|Dalgin, Gokhan - HARVARD SPH|
|Hotamisligil, Gokhan - HARVARD SPH|
Submitted to: Molecular and Cellular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 1, 2004
Publication Date: January 20, 2005
Citation: Tong, Q., Tsai, J., Tan, G., Dalgin, G., Hotamisligil, G.S. 2005. Interaction between GATA and the C/EBP family of transcription factors is critical in GATA-mediated supression of adipocyte differentiation. Molecular and Cellular Biology. 25(2):706-715. Interpretive Summary: We have previously reported that GATA-2 and GATA-3 transcription factors suppress fat cell formation by inhibiting the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma), one of the key factors in promoting fat cell formation. In the present study, we demonstrate that both GATA-2 and GATA-3 form protein-protein interaction with C/EBP alpha and C/EBP beta transcription factors, two other key factors controlling fat cell formation. We determined the domains on C/EBP alpha and GATA-2 required for the interaction. We also found that disruption of the ability for GATA-2 to interact with C/EBP alpha also disrupts GATA's ability to suppress fat cell formation. Thus, we found GATA blocks fat cell formation through dual mechanisms by suppression on PPAR gamma and C/EBP alpha.
Technical 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 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/EBP beta, 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.