EBF2 determines and maintains brown adipocyte identity

TY - JOUR

T1 - EBF2 determines and maintains brown adipocyte identity

AU - Rajakumari, Sona

AU - Wu, Jun

AU - Ishibashi, Jeff

AU - Lim, Hee-Woong

AU - Giang, An-Hoa

AU - Won, Kyoung-Jae

AU - Reed, Randall R

AU - Seale, Patrick

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/4/2

Y1 - 2013/4/2

N2 - 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.

AB - 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.

KW - Adipocytes, Brown/cytology

KW - Animals

KW - Apoptosis

KW - Basic Helix-Loop-Helix Transcription Factors/deficiency

KW - Binding Sites

KW - Cells, Cultured

KW - DNA-Binding Proteins/genetics

KW - High-Throughput Nucleotide Sequencing

KW - Mice

KW - Mice, Knockout

KW - PPAR gamma/metabolism

KW - Protein Binding

KW - Protein Isoforms/metabolism

KW - Transcription Factors/genetics

KW - Transcription, Genetic

U2 - 10.1016/j.cmet.2013.01.015

DO - 10.1016/j.cmet.2013.01.015

M3 - Journal article

C2 - 23499423

SN - 1550-4131

VL - 17

SP - 562

EP - 574

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -