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
N1 - Publisher Copyright:
© 2018, The Author(s).
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 -