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Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat

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  • Fenfen Li

    (Georgia State University)

  • Jia Jing

    (Georgia State University)

  • Miranda Movahed

    (Georgia State University)

  • Xin Cui

    (Georgia State University)

  • Qiang Cao

    (Georgia State University)

  • Rui Wu

    (Georgia State University)

  • Ziyue Chen

    (Georgia State University)

  • Liqing Yu

    (University of Maryland School of Medicine)

  • Yi Pan

    (Georgia State University
    Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences)

  • Huidong Shi

    (Medical College of Georgia, Augusta University
    Medical College of Georgia, Augusta University)

  • Hang Shi

    (Georgia State University)

  • Bingzhong Xue

    (Georgia State University)

Abstract

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

Suggested Citation

  • Fenfen Li & Jia Jing & Miranda Movahed & Xin Cui & Qiang Cao & Rui Wu & Ziyue Chen & Liqing Yu & Yi Pan & Huidong Shi & Hang Shi & Bingzhong Xue, 2021. "Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat," Nature Communications, Nature, vol. 12(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27141-7
    DOI: 10.1038/s41467-021-27141-7
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    1. Yangmian Yuan & Yu Fan & Yihao Zhou & Rong Qiu & Wei Kang & Yu Liu & Yuchen Chen & Chenyu Wang & Jiajian Shi & Chengyu Liu & Yangkai Li & Min Wu & Kun Huang & Yong Liu & Ling Zheng, 2023. "Linker histone variant H1.2 is a brake on white adipose tissue browning," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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