LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation

Kotaro Anan, Shinjiro Hino, Noriaki Shimizu, Akihisa Sakamoto, Katsuya Nagaoka, Ryuta Takase, Kensaku Kohrogi, Hirotaka Araki, Yuko Hino, Shingo Usuki, Shinya Oki, Hirotoshi Tanaka, Kimitoshi Nakamura, Fumio Endo, Mitsuyoshi Nakao

研究成果: ジャーナルへの寄稿記事

4 引用 (Scopus)

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The metabolic properties of cells are formed under the influence of environmental factors such as nutrients and hormones. Although such a metabolic program is likely initiated through epigenetic mechanisms, the direct links between metabolic cues and activities of chromatin modifiers remain largely unknown. In this study, we show that lysine-specific demethylase-1 (LSD1) controls the metabolic program in myogenic differentiation, under the action of catabolic hormone, glucocorticoids. By using tran-scriptomic and epigenomic approaches, we revealed that LSD1 bound to oxidative metabolism and slow-twitch myosin genes, and repressed their expression. Consistent with this, loss of LSD1 activity during differentiation enhanced the oxidative capacity of myotubes. By testing the effects of various hormones, we found that LSD1 levels were decreased by treatment with the glucocorticoid dexamethasone (Dex) in cultured myoblasts and in skeletal muscle from mice. Mechanistically, glucocorticoid signaling induced expression of a ubiquitin E3 ligase, JADE-2, which was responsible for proteasomal degradation of LSD1. Consequently, in differentiating myoblasts, chemical inhibition of LSD1, in combination with Dex treatment, synergistically de-repressed oxidative metabolism genes, concomitant with increased histone H3 lysine 4 methylation at these loci. These findings demonstrated that LSD1 serves as an epigenetic regulator linking glucocorticoid action to metabolic programming during myogenic differentiation.

元の言語英語
ページ(範囲)5441-5454
ページ数14
ジャーナルNucleic acids research
46
発行部数11
DOI
出版物ステータス出版済み - 1 1 2018

All Science Journal Classification (ASJC) codes

  • Genetics

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    Anan, K., Hino, S., Shimizu, N., Sakamoto, A., Nagaoka, K., Takase, R., Kohrogi, K., Araki, H., Hino, Y., Usuki, S., Oki, S., Tanaka, H., Nakamura, K., Endo, F., & Nakao, M. (2018). LSD1 mediates metabolic reprogramming by glucocorticoids during myogenic differentiation. Nucleic acids research, 46(11), 5441-5454. https://doi.org/10.1093/nar/gky234