EBF2 Determines and Maintains Brown Adipocyte Identity

The master transcription factor Ppar gamma regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Ppar gamma also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Ppar gamma binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Ppar gamma 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 gamma target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppar gamma 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.