SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

Masatoshi Fukuda; Tatsuya Yoshizawa; Md Fazlul Karim; Shihab U. Sobuz; Wataru Korogi; Daiki Kobayasi; Hiroki Okanishi; Masayoshi Tasaki; Katsuhiko Ono; Tomohiro Sawa; Yoshifumi Sato; Mami Chirifu; Takeshi Masuda; Teruya Nakamura; Hironori Tanoue; Kazuhisa Nakashima; Yoshihiro Kobashigawa; Hiroshi Morioka; Eva Bober; Sumio Ohtsuki; Yuriko Yamagata; Yukio Ando; Yuichi Oike; Norie Araki; Shu Takeda; Hiroshi Mizuta; Kazuya Yamagata

doi:10.1038/s41467-018-05187-4

SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

Masatoshi Fukuda
, Tatsuya Yoshizawa
, Md Fazlul Karim
, Shihab U. Sobuz
, Wataru Korogi
, Daiki Kobayasi
, Hiroki Okanishi
, Masayoshi Tasaki
, Katsuhiko Ono
, Tomohiro Sawa
, Yoshifumi Sato
, Mami Chirifu
, Takeshi Masuda
, Teruya Nakamura
, Hironori Tanoue
, Kazuhisa Nakashima
, Yoshihiro Kobashigawa
, Hiroshi Morioka
, Eva Bober
, Sumio Ohtsuki

Yuriko Yamagata, Yukio Ando, Yuichi Oike, Norie Araki, Shu Takeda, Hiroshi Mizuta, Kazuya Yamagata

Research output: Contribution to journal › Article › peer-review

105 Citations (Scopus)

Abstract

SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.

Original language	English
Article number	2833
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-05187-4
Publication status	Published - 01-12-2018
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-018-05187-4

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Fukuda, M., Yoshizawa, T., Karim, M. F., Sobuz, S. U., Korogi, W., Kobayasi, D., Okanishi, H., Tasaki, M., Ono, K., Sawa, T., Sato, Y., Chirifu, M., Masuda, T., Nakamura, T., Tanoue, H., Nakashima, K., Kobashigawa, Y., Morioka, H., Bober, E., ... Yamagata, K. (2018). SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix. Nature communications, 9(1), Article 2833. https://doi.org/10.1038/s41467-018-05187-4

@article{4ed81ecb57c0436fb72ef4131314717c,

title = "SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix",

abstract = "SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.",

author = "Masatoshi Fukuda and Tatsuya Yoshizawa and Karim, \{Md Fazlul\} and Sobuz, \{Shihab U.\} and Wataru Korogi and Daiki Kobayasi and Hiroki Okanishi and Masayoshi Tasaki and Katsuhiko Ono and Tomohiro Sawa and Yoshifumi Sato and Mami Chirifu and Takeshi Masuda and Teruya Nakamura and Hironori Tanoue and Kazuhisa Nakashima and Yoshihiro Kobashigawa and Hiroshi Morioka and Eva Bober and Sumio Ohtsuki and Yuriko Yamagata and Yukio Ando and Yuichi Oike and Norie Araki and Shu Takeda and Hiroshi Mizuta and Kazuya Yamagata",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s).",

year = "2018",

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doi = "10.1038/s41467-018-05187-4",

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Fukuda, M, Yoshizawa, T, Karim, MF, Sobuz, SU, Korogi, W, Kobayasi, D, Okanishi, H, Tasaki, M, Ono, K, Sawa, T, Sato, Y, Chirifu, M, Masuda, T, Nakamura, T, Tanoue, H, Nakashima, K, Kobashigawa, Y, Morioka, H, Bober, E, Ohtsuki, S, Yamagata, Y, Ando, Y, Oike, Y, Araki, N, Takeda, S, Mizuta, H & Yamagata, K 2018, 'SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix', Nature communications, vol. 9, no. 1, 2833. https://doi.org/10.1038/s41467-018-05187-4

TY - JOUR

T1 - SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

AU - Fukuda, Masatoshi

AU - Yoshizawa, Tatsuya

AU - Karim, Md Fazlul

AU - Sobuz, Shihab U.

AU - Korogi, Wataru

AU - Kobayasi, Daiki

AU - Okanishi, Hiroki

AU - Tasaki, Masayoshi

AU - Ono, Katsuhiko

AU - Sawa, Tomohiro

AU - Sato, Yoshifumi

AU - Chirifu, Mami

AU - Masuda, Takeshi

AU - Nakamura, Teruya

AU - Tanoue, Hironori

AU - Nakashima, Kazuhisa

AU - Kobashigawa, Yoshihiro

AU - Morioka, Hiroshi

AU - Bober, Eva

AU - Ohtsuki, Sumio

AU - Yamagata, Yuriko

AU - Ando, Yukio

AU - Oike, Yuichi

AU - Araki, Norie

AU - Takeda, Shu

AU - Mizuta, Hiroshi

AU - Yamagata, Kazuya

PY - 2018/12/1

Y1 - 2018/12/1

N2 - SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.

AB - SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.

UR - https://www.scopus.com/pages/publications/85050596236

UR - https://www.scopus.com/pages/publications/85050596236#tab=citedBy

U2 - 10.1038/s41467-018-05187-4

DO - 10.1038/s41467-018-05187-4

M3 - Article

C2 - 30026585

AN - SCOPUS:85050596236

SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 2833

ER -

SIRT7 has a critical role in bone formation by regulating lysine acylation of SP7/Osterix

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