Abstract
The master transcription factor Pparγ regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Pparγ also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Pparγ binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif 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 adipose-specific Pparγ target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Pparγ 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.
| Original language | English |
|---|---|
| Journal | Cell Metabolism |
| Volume | 17 |
| Issue number | 4 |
| Pages (from-to) | 562-74 |
| Number of pages | 13 |
| ISSN | 1550-4131 |
| DOIs | |
| Publication status | Published - 2 Apr 2013 |
| Externally published | Yes |
Keywords
- Adipocytes, Brown/cytology
- Animals
- Apoptosis
- Basic Helix-Loop-Helix Transcription Factors/deficiency
- Binding Sites
- Cells, Cultured
- DNA-Binding Proteins/genetics
- High-Throughput Nucleotide Sequencing
- Mice
- Mice, Knockout
- PPAR gamma/metabolism
- Protein Binding
- Protein Isoforms/metabolism
- Transcription Factors/genetics
- Transcription, Genetic