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lüll EBF2 determines and maintains brown adipocyte identity Rajakumari S; Wu J; Ishibashi J; Lim HW; Giang AH; Won KJ; Reed RR; Seale PCell Metab 2013[Apr]; 17 (4): 562-74The master transcription factor Ppargamma regulates the general differentiation program of both brown and white adipocytes. However, it has been unclear whether Ppargamma also controls fat lineage-specific characteristics. Here, we show that early B cell factor-2 (Ebf2) regulates Ppargamma binding activity to determine brown versus white adipocyte identity. The Ebf DNA-binding motif was highly enriched within brown adipose-specific Ppargamma 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 Ppargamma target genes. When expressed in myoblasts or white preadipose cells, Ebf2 recruited Ppargamma 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.|Adipocytes, Brown/cytology/*metabolism[MESH]|Animals[MESH]|Apoptosis[MESH]|Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/*metabolism[MESH]|Binding Sites[MESH]|Cells, Cultured[MESH]|DNA-Binding Proteins/genetics/metabolism[MESH]|High-Throughput Nucleotide Sequencing[MESH]|Mice[MESH]|Mice, Knockout[MESH]|PPAR gamma/metabolism[MESH]|Protein Binding[MESH]|Protein Isoforms/metabolism[MESH]|Transcription Factors/genetics/metabolism[MESH]|Transcription, Genetic[MESH] |