title: EBF2 determines and maintains brown adipocyte identity.
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.
authors.affiliation: Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Sona
authors.initials: S
authors.lastname: Rajakumari
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jeff
authors.initials: J
authors.lastname: Ishibashi
authors.forename: Hee-Woong
authors.initials: HW
authors.lastname: Lim
authors.forename: An-Hoa
authors.initials: AH
authors.lastname: Giang
authors.forename: Kyoung-Jae
authors.initials: KJ
authors.lastname: Won
authors.forename: Randall R
authors.initials: RR
authors.lastname: Reed
authors.forename: Patrick
authors.initials: P
authors.lastname: Seale
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D047495:PPAR gamma; D020033:Protein Isoforms; D014157:Transcription Factors; C489922:Ebf2 protein, mouse; C521133:Prdm16 protein, mouse