Spatiotemporal dynamics of SETD5-containing NCoR–HDAC3 complex determines enhancer activation for adipogenesis

Yoshihiro Matsumura (), Ryo Ito, Ayumu Yajima, Rei Yamaguchi, Toshiya Tanaka, Takeshi Kawamura, Kenta Magoori, Yohei Abe, Aoi Uchida, Takeshi Yoneshiro, Hiroyuki Hirakawa, Ji Zhang, Makoto Arai, Chaoran Yang, Ge Yang, Hiroki Takahashi, Hitomi Fujihashi, Ryo Nakaki, Shogo Yamamoto, Satoshi Ota, Shuichi Tsutsumi, Shin-ichi Inoue, Hiroshi Kimura, Youichiro Wada, Tatsuhiko Kodama, Takeshi Inagaki, Timothy F. Osborne, Hiroyuki Aburatani, Koichi Node and Juro Sakai ()
Additional contact information
Yoshihiro Matsumura: The University of Tokyo
Ryo Ito: Tohoku University Graduate School of Medicine
Ayumu Yajima: The University of Tokyo
Rei Yamaguchi: Tohoku University Graduate School of Medicine
Toshiya Tanaka: The University of Tokyo
Takeshi Kawamura: The University of Tokyo
Kenta Magoori: The University of Tokyo
Yohei Abe: The University of Tokyo
Aoi Uchida: The University of Tokyo
Takeshi Yoneshiro: The University of Tokyo
Hiroyuki Hirakawa: The University of Tokyo
Ji Zhang: The University of Tokyo
Makoto Arai: The University of Tokyo
Chaoran Yang: Tohoku University Graduate School of Medicine
Ge Yang: Tohoku University Graduate School of Medicine
Hiroki Takahashi: Tohoku University Graduate School of Medicine
Hitomi Fujihashi: The University of Tokyo
Ryo Nakaki: The University of Tokyo
Shogo Yamamoto: The University of Tokyo
Satoshi Ota: The University of Tokyo
Shuichi Tsutsumi: The University of Tokyo
Shin-ichi Inoue: Tohoku University Graduate School of Medicine
Hiroshi Kimura: Tokyo Institute of Technology
Youichiro Wada: The University of Tokyo
Tatsuhiko Kodama: The University of Tokyo
Takeshi Inagaki: The University of Tokyo
Timothy F. Osborne: Diabetes and Metabolism of the Johns Hopkins University School of Medicine
Hiroyuki Aburatani: The University of Tokyo
Koichi Node: Saga University
Juro Sakai: The University of Tokyo

Nature Communications, 2021, vol. 12, issue 1, 1-19

Abstract: Abstract Enhancer activation is essential for cell-type specific gene expression during cellular differentiation, however, how enhancers transition from a hypoacetylated “primed” state to a hyperacetylated-active state is incompletely understood. Here, we show SET domain-containing 5 (SETD5) forms a complex with NCoR-HDAC3 co-repressor that prevents histone acetylation of enhancers for two master adipogenic regulatory genes Cebpa and Pparg early during adipogenesis. The loss of SETD5 from the complex is followed by enhancer hyperacetylation. SETD5 protein levels were transiently increased and rapidly degraded prior to enhancer activation providing a mechanism for the loss of SETD5 during the transition. We show that induction of the CDC20 co-activator of the ubiquitin ligase leads to APC/C mediated degradation of SETD5 during the transition and this operates as a molecular switch that facilitates adipogenesis.

Date: 2021
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Citations: View citations in EconPapers (3)

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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27321-5

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DOI: 10.1038/s41467-021-27321-5

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