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NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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  • Yuta Hiraike
  • Hironori Waki
  • Jing Yu
  • Masahiro Nakamura
  • Kana Miyake
  • Gaku Nagano
  • Ryo Nakaki
  • Ken Suzuki
  • Hirofumi Kobayashi
  • Shogo Yamamoto
  • Wei Sun
  • Tomohisa Aoyama
  • Yusuke Hirota
  • Haruya Ohno
  • Kenji Oki
  • Masayasu Yoneda
  • Andrew P White
  • Yu-Hua Tseng
  • Aaron M Cypess
  • Therese J Larsen
  • Naja Z Jespersen
  • Camilla Scheele
  • Shuichi Tsutsumi
  • Hiroyuki Aburatani
  • Toshimasa Yamauchi
  • Takashi Kadowaki
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Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription. Introduction of NFIA into myoblasts results in brown adipocyte differentiation. Conversely, the brown fat of NFIA-knockout mice displays impaired expression of the brown-fat-specific genes and reciprocal elevation of muscle genes. Finally, expression of NFIA and the brown-fat-specific genes is positively correlated in human brown fat. These results indicate that NFIA activates the cell-type-specific enhancers and facilitates the binding of PPARγ to control the brown fat gene program.

OriginalsprogEngelsk
TidsskriftNature Cell Biology
Vol/bind19
Udgave nummer9
Sider (fra-til)1081-1092
Antal sider12
ISSN1465-7392
DOI
StatusUdgivet - sep. 2017

ID: 52607727