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Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins

Author

Listed:
  • Ravikanth Nanduri

    (National Institutes of Health)

  • Takashi Furusawa

    (National Institutes of Health)

  • Alexei Lobanov

    (National Institutes of Health)

  • Bing He

    (National Institutes of Health)

  • Carol Xie

    (National Institutes of Health)

  • Kimia Dadkhah

    (Frederick National Laboratory for Cancer Research)

  • Michael C. Kelly

    (Frederick National Laboratory for Cancer Research)

  • Oksana Gavrilova

    (National Institutes of Health)

  • Frank J. Gonzalez

    (National Institutes of Health)

  • Michael Bustin

    (National Institutes of Health)

Abstract

White adipose tissue browning is a key metabolic process controlled by epigenetic factors that facilitate changes in gene expression leading to altered cell identity. We find that male mice lacking the nucleosome binding proteins HMGN1 and HMGN2 (DKO mice), show decreased body weight and inguinal WAT mass, but elevated food intake, WAT browning and energy expenditure. DKO white preadipocytes show reduced chromatin accessibility and lower FRA2 and JUN binding at Pparγ and Pparα promoters. White preadipocytes and mouse embryonic fibroblasts from DKO mice show enhanced rate of differentiation into brown-like adipocytes. Differentiating DKO adipocytes show reduced H3K27ac levels at white adipocyte-specific enhancers but elevated H3K27ac levels at brown adipocyte-specific enhancers, suggesting a faster rate of change in cell identity, from white to brown-like adipocytes. Thus, HMGN proteins function as epigenetic factors that stabilize white adipocyte cell identity, thereby modulating the rate of white adipose tissue browning and affecting energy metabolism in mice.

Suggested Citation

  • Ravikanth Nanduri & Takashi Furusawa & Alexei Lobanov & Bing He & Carol Xie & Kimia Dadkhah & Michael C. Kelly & Oksana Gavrilova & Frank J. Gonzalez & Michael Bustin, 2022. "Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34964-5
    DOI: 10.1038/s41467-022-34964-5
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    References listed on IDEAS

    as
    1. Evan D. Rosen & Bruce M. Spiegelman, 2006. "Adipocytes as regulators of energy balance and glucose homeostasis," Nature, Nature, vol. 444(7121), pages 847-853, December.
    2. Bing He & Tao Deng & Iris Zhu & Takashi Furusawa & Shaofei Zhang & Wei Tang & Yuri Postnikov & Stefan Ambs & Caiyi Cherry Li & Ferenc Livak & David Landsman & Michael Bustin, 2018. "Binding of HMGN proteins to cell specific enhancers stabilizes cell identity," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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