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BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning

Author

Listed:
  • Tongyu Liu

    (University of Michigan
    University of Michigan)

  • Lin Mi

    (University of Michigan)

  • Jing Xiong

    (University of Michigan)

  • Peter Orchard

    (University of Michigan
    University of Michigan)

  • Qi Yu

    (University of Michigan)

  • Lei Yu

    (University of Michigan)

  • Xu-Yun Zhao

    (University of Michigan)

  • Zhuo-Xian Meng

    (Key Laboratory of Disease Proteomics of Zhejiang Province
    Zhejiang University)

  • Stephen C. J. Parker

    (University of Michigan
    University of Michigan)

  • Jiandie D. Lin

    (University of Michigan)

  • Siming Li

    (University of Michigan)

Abstract

Brown and beige fat share a remarkably similar transcriptional program that supports fuel oxidation and thermogenesis. The chromatin-remodeling machinery that governs genome accessibility and renders adipocytes poised for thermogenic activation remains elusive. Here we show that BAF60a, a subunit of the SWI/SNF chromatin-remodeling complexes, serves an indispensable role in cold-induced thermogenesis in brown fat. BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes. Surprisingly, fat-specific BAF60a inactivation triggers more pronounced cold-induced browning of inguinal white adipose tissue that is linked to induction of MC2R, a receptor for the pituitary hormone ACTH. Elevated MC2R expression sensitizes adipocytes and BAF60a-deficient adipose tissue to thermogenic activation in response to ACTH stimulation. These observations reveal an unexpected dichotomous role of BAF60a-mediated chromatin remodeling in transcriptional control of brown and beige gene programs and illustrate a pituitary-adipose signaling axis in the control of thermogenesis.

Suggested Citation

  • Tongyu Liu & Lin Mi & Jing Xiong & Peter Orchard & Qi Yu & Lei Yu & Xu-Yun Zhao & Zhuo-Xian Meng & Stephen C. J. Parker & Jiandie D. Lin & Siming Li, 2020. "BAF60a deficiency uncouples chromatin accessibility and cold sensitivity from white fat browning," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16148-1
    DOI: 10.1038/s41467-020-16148-1
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