NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program
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NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program. / Hiraike, Yuta; Waki, Hironori; Yu, Jing; Nakamura, Masahiro; Miyake, Kana; Nagano, Gaku; Nakaki, Ryo; Suzuki, Ken; Kobayashi, Hirofumi; Yamamoto, Shogo; Sun, Wei; Aoyama, Tomohisa; Hirota, Yusuke; Ohno, Haruya; Oki, Kenji; Yoneda, Masayasu; White, Andrew P; Tseng, Yu-Hua; Cypess, Aaron M; Larsen, Therese J; Jespersen, Naja Z; Scheele, Camilla; Tsutsumi, Shuichi; Aburatani, Hiroyuki; Yamauchi, Toshimasa; Kadowaki, Takashi.
In: Nature Cell Biology, Vol. 19, No. 9, 09.2017, p. 1081-1092.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program
AU - Hiraike, Yuta
AU - Waki, Hironori
AU - Yu, Jing
AU - Nakamura, Masahiro
AU - Miyake, Kana
AU - Nagano, Gaku
AU - Nakaki, Ryo
AU - Suzuki, Ken
AU - Kobayashi, Hirofumi
AU - Yamamoto, Shogo
AU - Sun, Wei
AU - Aoyama, Tomohisa
AU - Hirota, Yusuke
AU - Ohno, Haruya
AU - Oki, Kenji
AU - Yoneda, Masayasu
AU - White, Andrew P
AU - Tseng, Yu-Hua
AU - Cypess, Aaron M
AU - Larsen, Therese J
AU - Jespersen, Naja Z
AU - Scheele, Camilla
AU - Tsutsumi, Shuichi
AU - Aburatani, Hiroyuki
AU - Yamauchi, Toshimasa
AU - Kadowaki, Takashi
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/ncb3590
DO - 10.1038/ncb3590
M3 - Journal article
C2 - 28812581
VL - 19
SP - 1081
EP - 1092
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 9
ER -
ID: 182619023