EBF2 determines and maintains brown adipocyte identity.

ABSTRACT: 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.

SUBMITTER: Rajakumari S 

PROVIDER: S-EPMC3622114 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature