EBF2 determines and maintains brown adipocyte identity.
Cell Metab, 2013/4/02;17(4):562-74.
Rajakumari S[1], Wu J, Ishibashi J, Lim HW, Giang AH, Won KJ, Reed RR, Seale P
Affiliations
PMID: 23499423
Impact factor: 31.373
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.
MeSH terms
Adipocytes, Brown; Animals; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Binding Sites; Cells, Cultured; DNA-Binding Proteins; High-Throughput Nucleotide Sequencing; Mice; Mice, Knockout; PPAR gamma; Protein Binding; Protein Isoforms; Transcription Factors; Transcription, Genetic
More resources
Full text:
Europe PubMed Central; PubMed Central
EndNote: Download