3 years ago

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

NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program
Kenji Oki, Ken Suzuki, Shuichi Tsutsumi, Hironori Waki, Hirofumi Kobayashi, Masayasu Yoneda, Yuta Hiraike, Naja Z. Jespersen, Haruya Ohno, Masahiro Nakamura, Camilla Scheele, Tomohisa Aoyama, Kana Miyake, Therese J. Larsen, Takashi Kadowaki, Toshimasa Yamauchi, Shogo Yamamoto, Jing Yu, Yusuke Hirota, Aaron M. Cypess, Wei Sun, Hiroyuki Aburatani, Yu-Hua Tseng, Gaku Nagano, Ryo Nakaki, Andrew P. White
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.

Publisher URL: http://dx.doi.org/10.1038/ncb3590

DOI: 10.1038/ncb3590

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