EBF2 determines and maintains brown adipocyte identity.

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 pre-adipose 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.

主转录因子过氧化物酶体增殖物激活受体γ（Pparγ）调节棕色和白色脂肪细胞的总体分化程序。然而，Pparγ是否也控制脂肪谱系特异性特征一直不清楚。在此，我们表明早期B细胞因子2（Ebf2）调节Pparγ结合活性以确定棕色与白色脂肪细胞的特性。我们通过全基因组染色质免疫沉淀测序（ChIP - Seq）鉴定出，Ebf DNA结合基序在棕色脂肪特异性Pparγ结合位点内高度富集。在Ebf异构体中，相对于白色脂肪细胞，Ebf2在棕色脂肪细胞中选择性表达，并结合在棕色脂肪特异性Pparγ靶基因上。当在成肌细胞或白色前脂肪细胞中表达时，Ebf2将Pparγ招募到其棕色选择性结合位点，并将细胞重编程为棕色脂肪命运。来自Ebf2缺陷小鼠的棕色脂肪细胞和组织显示出棕色特异性特征和产热能力的丧失。总之，这些结果确定Ebf2是棕色脂肪细胞命运和功能的关键转录调节因子。