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CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling

Author

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  • Caojie Liu

    (West China Hospital of Stomatology, Sichuan University)

  • Qiuchan Xiong

    (West China Hospital of Stomatology, Sichuan University)

  • Qiwen Li

    (West China Hospital of Stomatology, Sichuan University)

  • Weimin Lin

    (West China Hospital of Stomatology, Sichuan University)

  • Shuang Jiang

    (West China Hospital of Stomatology, Sichuan University)

  • Danting Zhang

    (West China Hospital of Stomatology, Sichuan University)

  • Yuan Wang

    (West China Hospital of Stomatology, Sichuan University)

  • Xiaobo Duan

    (West China Hospital of Stomatology, Sichuan University)

  • Ping Gong

    (West China Hospital of Stomatology, Sichuan University)

  • Ning Kang

    (West China Hospital of Stomatology, Sichuan University)

Abstract

Chromodomain helicase DNA-binding protein 7 (CHD7), an ATP-dependent eukaryotic chromatin remodeling enzyme, is essential for the development of organs. The mutation of CHD7 is the main cause of CHARGE syndrome, but its function and mechanism in skeletal system remain unclear. Here, we show conditional knockout of Chd7 in bone marrow mesenchymal stem cells (MSCs) and preosteoblasts leads to a pathological phenotype manifested as low bone mass and severely high marrow adiposity. Mechanistically, we identify enhancement of the peroxisome proliferator-activated receptor (PPAR) signaling in Chd7-deficient MSCs. Loss of Chd7 reduces the restriction of PPAR-γ and then PPAR-γ associates with trimethylated histone H3 at lysine 4 (H3K4me3), which subsequently activates the transcription of downstream adipogenic genes and disrupts the balance between osteogenic and adipogenic differentiation. Our data illustrate the pathological manifestations of Chd7 mutation in MSCs and reveal an epigenetic mechanism in skeletal health and diseases.

Suggested Citation

  • Caojie Liu & Qiuchan Xiong & Qiwen Li & Weimin Lin & Shuang Jiang & Danting Zhang & Yuan Wang & Xiaobo Duan & Ping Gong & Ning Kang, 2022. "CHD7 regulates bone-fat balance by suppressing PPAR-γ signaling," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29633-6
    DOI: 10.1038/s41467-022-29633-6
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