EBF2 determines and maintains brown adipocyte identity

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Sona Rajakumari
  • Jun Wu
  • Jeff Ishibashi
  • Hee-Woong Lim
  • An-Hoa Giang
  • Kyoung-Jae Won
  • Randall R Reed
  • Patrick Seale

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.

OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind17
Udgave nummer4
Sider (fra-til)562-74
Antal sider13
ISSN1550-4131
DOI
StatusUdgivet - 2 apr. 2013
Eksternt udgivetJa

ID: 199332545