Authors:
Sona Rajakumari, Jun Wu, Jeff Ishibashi, Hee-Woong Lim, An-Hoa Giang, Kyoung-Jae Won, Randall R. Reed, & Patrick Seale
Summary:
The master transcription factor Ppar regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Ppar also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Ppar binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Ppar 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 adipose-specific Ppar target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppar to its brown-selective binding sites and reprogrammed cells to a brown fat fate. Brown adipose cells and tissue from Ebf2-deficient mice displayed a loss of brown-specific characteristics and thermogenic capacity. Together, these results identify Ebf2 as a key transcriptional regulator of brown fat cell fate and function.
Source:
Cell Metabolism; (03/14/13)