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Molecular and Cellular Biology, January 2007, p. 743-757, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01557-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Critical Role for Ebf1 and Ebf2 in the Adipogenic Transcriptional Cascade{triangledown} ,{dagger}

Maria A. Jimenez,1,2 Peter Åkerblad,3 Mikael Sigvardsson,4 and Evan D. Rosen1,2*

Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts,1 Broad Institute of Harvard and MIT, Cambridge, Massachusetts,2 Astra Zeneca R&D, Mölndal, Sweden,3 Department of Stem Cell Biology, Lund University, Lund, Sweden4

Received 21 August 2006/ Accepted 10 October 2006

The Ebf (O/E) family of helix-loop-helix transcription factors plays a significant role in B lymphocyte and neuronal development. The three primary members of this family, Ebf1, 2, and 3, are all expressed in adipocytes, and Ebf1 promotes adipogenesis when overexpressed in NIH 3T3 fibroblasts. Here we report that these three proteins have adipogenic potential in multiple cellular models and that peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is required for this effect, at least in part due to direct activation of the PPAR{gamma}1 promoter by Ebf1. Ebf1 also directly binds to and activates the C/EBP{alpha} promoter, which exerts positive feedback on C/EBP{delta} expression. Despite this, C/EBP{alpha} is dispensable for the adipogenic action of Ebf proteins. Ebf1 itself is induced by C/EBPß and {delta}, which bind and activate its promoter. Reduction of Ebf1 and Ebf2 proteins by specific short hairpin RNA blocks differentiation of 3T3-L1 cells, suggesting a critical role for these factors and the absence of functional redundancy between members of this family. Altogether, these data place Ebf1 within the known transcriptional cascade of adipogenesis and suggest critical roles for Ebf1 and Ebf2.

* Corresponding author. Mailing address: Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215. Phone: (617) 667-3221. Fax: (617) 667-2927. E-mail: erosen{at}bidmc.harvard.edu.

{triangledown} Published ahead of print on 23 October 2006.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, January 2007, p. 743-757, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01557-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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