Transcriptional control of brown adipocyte development

The Royal Society (ME 2012) (2012) Proc Physiol Soc 29, SA03

Research Symposium: Transcriptional control of brown adipocyte development

S. Rajakumari1, J. Wu1, J. Ishibashi1, M. Harms1, K. Won1, L. Hee-Woong1, P. Seale1

1. Cell & Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

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The differentiation of both brown (heat-producing) and white (energy storing) adipocytes is regulated by the master transcription factor Pparγ. While Pparγ can explain the characteristics that are common to the two types of fat cells, it remains unclear whether Pparγ also controls lineage-specific gene programs. Here, we show that Early B-Cell Factor-2 (Ebf2) determines brown versus white adipocyte identity. A binding motif for Ebf was highly enriched within brown adipose-specific Pparγ binding sites that we identified by genome-wide ChIP-Seq. Of the Ebf isoforms, Ebf2 was selectively expressed in brown relative to white adipocytes and was bound at brown fat-specific Pparγ target genes. Strikingly, Ebf2 expression in myoblasts or white pre-adipose cells recruited Pparγ to brown-selective binding sites and reprogrammed cells to a brown fat fate. Notably, Ebf2 and Pparγ cooperated to directly and powerfully activate transcription of Prdm16, a key regulator of thermogenic genes. In brown fat cells, Ebf2 expression was essential for establishing and maintaining a brown fat-specific gene program. Finally, the presumptive brown adipose tissue in Ebf2-deficient mice was completely devoid of brown character and had a molecular profile resembling white fat. Taken together, these results show that Ebf2 determines brown adipocyte identity.



Where applicable, experiments conform with Society ethical requirements.

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