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MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis

Author

Listed:
  • Hiroki Takahashi

    (Tohoku University Graduate School of Medicine
    The University of Tokyo)

  • Ge Yang

    (Tohoku University Graduate School of Medicine)

  • Takeshi Yoneshiro

    (The University of Tokyo)

  • Yohei Abe

    (The University of Tokyo)

  • Ryo Ito

    (Tohoku University Graduate School of Medicine)

  • Chaoran Yang

    (Tohoku University Graduate School of Medicine)

  • Junna Nakazono

    (Kyoto University)

  • Mayumi Okamoto-Katsuyama

    (The University of Tokyo)

  • Aoi Uchida

    (The University of Tokyo)

  • Makoto Arai

    (Tohoku University Graduate School of Medicine)

  • Hitomi Jin

    (Tohoku University Graduate School of Medicine)

  • Hyunmi Choi

    (Tohoku University Graduate School of Medicine)

  • Myagmar Tumenjargal

    (Tohoku University Graduate School of Medicine)

  • Shiyu Xie

    (Tohoku University Graduate School of Medicine)

  • Ji Zhang

    (Tohoku University Graduate School of Medicine)

  • Hina Sagae

    (Tohoku University Graduate School of Medicine)

  • Yanan Zhao

    (Tohoku University Graduate School of Medicine)

  • Rei Yamaguchi

    (Tohoku University Graduate School of Medicine)

  • Yu Nomura

    (Tohoku University Graduate School of Medicine)

  • Yuichi Shimizu

    (Tohoku University Graduate School of Medicine)

  • Kaito Yamada

    (Tohoku University Graduate School of Medicine
    Tohoku University Graduate School of Medicine)

  • Satoshi Yasuda

    (Tohoku University Graduate School of Medicine)

  • Hiroshi Kimura

    (Tokyo Institute of Technology)

  • Toshiya Tanaka

    (The University of Tokyo)

  • Youichiro Wada

    (The University of Tokyo)

  • Tatsuhiko Kodama

    (The University of Tokyo)

  • Hiroyuki Aburatani

    (The University of Tokyo)

  • Min-Sheng Zhu

    (Nanjing University)

  • Takeshi Inagaki

    (The University of Tokyo
    Gunma University)

  • Timothy F. Osborne

    (Diabetes and Metabolism of the Johns Hopkins University School of Medicine)

  • Takeshi Kawamura

    (The University of Tokyo)

  • Yasushi Ishihama

    (Kyoto University)

  • Yoshihiro Matsumura

    (Tohoku University Graduate School of Medicine
    The University of Tokyo)

  • Juro Sakai

    (Tohoku University Graduate School of Medicine
    The University of Tokyo)

Abstract

Protein kinase A promotes beige adipogenesis downstream from β-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1β (MYPT1-PP1β) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1β depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1β also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.

Suggested Citation

  • Hiroki Takahashi & Ge Yang & Takeshi Yoneshiro & Yohei Abe & Ryo Ito & Chaoran Yang & Junna Nakazono & Mayumi Okamoto-Katsuyama & Aoi Uchida & Makoto Arai & Hitomi Jin & Hyunmi Choi & Myagmar Tumenjar, 2022. "MYPT1-PP1β phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33363-0
    DOI: 10.1038/s41467-022-33363-0
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    References listed on IDEAS

    as
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