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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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    as
    1. Ruby Yu & Xiaoyi Wang & Danesh Moazed, 2018. "Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation," Nature, Nature, vol. 558(7711), pages 615-619, June.
    2. Sito Torres-Garcia & Imtiyaz Yaseen & Manu Shukla & Pauline N. C. B. Audergon & Sharon A. White & Alison L. Pidoux & Robin C. Allshire, 2020. "Epigenetic gene silencing by heterochromatin primes fungal resistance," Nature, Nature, vol. 585(7825), pages 453-458, September.
    3. Gloria Jih & Nahid Iglesias & Mark A. Currie & Natarajan V. Bhanu & Joao A. Paulo & Steven P. Gygi & Benjamin A. Garcia & Danesh Moazed, 2017. "Unique roles for histone H3K9me states in RNAi and heritable silencing of transcription," Nature, Nature, vol. 547(7664), pages 463-467, July.
    4. Ruchi Bajpai & Denise A. Chen & Alvaro Rada-Iglesias & Junmei Zhang & Yiqin Xiong & Jill Helms & Ching-Pin Chang & Yingming Zhao & Tomek Swigut & Joanna Wysocka, 2010. "CHD7 cooperates with PBAF to control multipotent neural crest formation," Nature, Nature, vol. 463(7283), pages 958-962, February.
    5. Nick van Gastel & Steve Stegen & Guy Eelen & Sandra Schoors & Aurélie Carlier & Veerle W. Daniëls & Ninib Baryawno & Dariusz Przybylski & Maarten Depypere & Pieter-Jan Stiers & Dennis Lambrechts & Rie, 2020. "Lipid availability determines fate of skeletal progenitor cells via SOX9," Nature, Nature, vol. 579(7797), pages 111-117, March.
    6. Yunshu Wu & Liang Xie & Mengyuan Wang & Qiuchan Xiong & Yuchen Guo & Yu Liang & Jing Li & Rui Sheng & Peng Deng & Yuan Wang & Rixin Zheng & Yizhou Jiang & Ling Ye & Qianming Chen & Xuedong Zhou & Shui, 2018. "Mettl3-mediated m6A RNA methylation regulates the fate of bone marrow mesenchymal stem cells and osteoporosis," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    7. Daphne S. Cabianca & Celia Muñoz-Jiménez & Véronique Kalck & Dimos Gaidatzis & Jan Padeken & Andrew Seeber & Peter Askjaer & Susan M. Gasser, 2019. "Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nuclei," Nature, Nature, vol. 569(7758), pages 734-739, May.
    8. Yuan Wang & Peng Deng & Yuting Liu & Yunshu Wu & Yaqian Chen & Yuchen Guo & Shiwen Zhang & Xiaofei Zheng & Liyan Zhou & Weiqing Liu & Qiwen Li & Weimin Lin & Xingying Qi & Guomin Ou & Cunyu Wang & Qua, 2020. "Alpha-ketoglutarate ameliorates age-related osteoporosis via regulating histone methylations," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    9. Magdalena B. Rother & Stefania Pellegrino & Rebecca Smith & Marco Gatti & Cornelia Meisenberg & Wouter W. Wiegant & Martijn S. Luijsterburg & Ralph Imhof & Jessica A. Downs & Alfred C. O. Vertegaal & , 2020. "CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    10. Gang G. Wang & Jikui Song & Zhanxin Wang & Holger L. Dormann & Fabio Casadio & Haitao Li & Jun-Li Luo & Dinshaw J. Patel & C. David Allis, 2009. "Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger," Nature, Nature, vol. 459(7248), pages 847-851, June.
    11. John F. Flanagan & Li-Zhi Mi & Maksymilian Chruszcz & Marcin Cymborowski & Katrina L. Clines & Youngchang Kim & Wladek Minor & Fraydoon Rastinejad & Sepideh Khorasanizadeh, 2005. "Double chromodomains cooperate to recognize the methylated histone H3 tail," Nature, Nature, vol. 438(7071), pages 1181-1185, December.
    12. Jeanine L. Van Nostrand & Colleen A. Brady & Heiyoun Jung & Daniel R. Fuentes & Margaret M. Kozak & Thomas M. Johnson & Chieh-Yu Lin & Chien-Jung Lin & Donald L. Swiderski & Hannes Vogel & Jonathan A., 2014. "Inappropriate p53 activation during development induces features of CHARGE syndrome," Nature, Nature, vol. 514(7521), pages 228-232, October.
    13. Weijun Feng & Daisuke Kawauchi & Huiqin Körkel-Qu & Huan Deng & Elisabeth Serger & Laura Sieber & Jenna Ariel Lieberman & Silvia Jimeno-González & Sander Lambo & Bola S. Hanna & Yassin Harim & Malin J, 2017. "Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    14. Erin D. Pleasance & Philip J. Stephens & Sarah O’Meara & David J. McBride & Alison Meynert & David Jones & Meng-Lay Lin & David Beare & King Wai Lau & Chris Greenman & Ignacio Varela & Serena Nik-Zain, 2010. "A small-cell lung cancer genome with complex signatures of tobacco exposure," Nature, Nature, vol. 463(7278), pages 184-190, January.
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