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

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

doi:10.1038/ncb3590

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

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 LarsenNaja Z Jespersen, Camilla Scheele, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki

27 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Nature Cell Biology
Volume	19
Issue number	9
Pages (from-to)	1081-1092
Number of pages	12
ISSN	1465-7392
DOIs	https://doi.org/10.1038/ncb3590
Publication status	Published - 1 Sept 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hiraike, Y., Waki, H., Yu, J., Nakamura, M., Miyake, K., Nagano, G., Nakaki, R., Suzuki, K., Kobayashi, H., Yamamoto, S., Sun, W., Aoyama, T., Hirota, Y., Ohno, H., Oki, K., Yoneda, M., White, A. P., Tseng, Y.-H., Cypess, A. M., ... Kadowaki, T. (2017). NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program. Nature Cell Biology, 19(9), 1081-1092. https://doi.org/10.1038/ncb3590

Hiraike, Y, Waki, H, Yu, J, Nakamura, M, Miyake, K, Nagano, G, Nakaki, R, Suzuki, K, Kobayashi, H, Yamamoto, S, Sun, W, Aoyama, T, Hirota, Y, Ohno, H, Oki, K, Yoneda, M, White, AP, Tseng, Y-H, Cypess, AM, Larsen, TJ, Jespersen, NZ, Scheele, C, Tsutsumi, S, Aburatani, H, Yamauchi, T & Kadowaki, T 2017, 'NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program', Nature Cell Biology, vol. 19, no. 9, pp. 1081-1092. https://doi.org/10.1038/ncb3590

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abstract = "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.",

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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

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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.

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

Abstract

Keywords

UN SDGs

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