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ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis

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  • Jiahui Du

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Yili Liu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Jinrui Sun

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Enhui Yao

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Jingyi Xu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Xiaolin Wu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Ling Xu

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Mingliang Zhou

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Guangzheng Yang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

  • Xinquan Jiang

    (Shanghai Jiao Tong University School of Medicine
    Shanghai Jiao Tong University
    Shanghai Engineering Research Center of Advanced Dental Technology and Materials)

Abstract

Chromatin remodeler ARID1A regulates gene transcription by modulating nucleosome positioning and chromatin accessibility. While ARID1A-mediated stage and lineage-restricted gene regulation during cell fate canalization remains unresolved. Using osteoclastogenesis as a model, we show that ARID1A transcriptionally safeguards the osteoclast (OC) fate canalization during proliferation-differentiation switching at single-cell resolution. Notably, ARID1A is indispensable for the transcriptional apparatus condensates formation with coactivator BRD4/lineage-specifying transcription factor (TF) PU.1 at Nfatc1 super-enhancer during safeguarding the OC fate canalization. Besides, the antagonist function between ARID1A-cBAF and BRD9-ncBAF complex during osteoclastogenesis has been validated with in vitro assay and compound mutant mouse model. Furthermore, the antagonistic function of ARID1A-“accelerator” and BRD9-“brake” both depend on coactivator BRD4-“clutch” during osteoclastogenesis. Overall, these results uncover sophisticated cooperation between chromatin remodeler ARID1A, coactivator, and lineage-specifying TF at super-enhancer of lineage master TF in a condensate manner, and antagonist between distinct BAF complexes in the proper and balanced cell fate canalization.

Suggested Citation

  • Jiahui Du & Yili Liu & Jinrui Sun & Enhui Yao & Jingyi Xu & Xiaolin Wu & Ling Xu & Mingliang Zhou & Guangzheng Yang & Xinquan Jiang, 2024. "ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50225-z
    DOI: 10.1038/s41467-024-50225-z
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