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TAF1 plays a critical role in AML1-ETO driven leukemogenesis

Author

Listed:
  • Ye Xu

    (University of Miami
    University of Miami)

  • Na Man

    (University of Miami
    University of Miami)

  • Daniel Karl

    (University of Miami
    University of Miami)

  • Concepcion Martinez

    (University of Miami
    University of Miami)

  • Fan Liu

    (University of Miami
    University of Miami)

  • Jun Sun

    (University of Miami
    University of Miami)

  • Camilo Jose Martinez

    (University of Miami
    University of Miami)

  • Gloria Mas Martin

    (University of Miami
    University of Miami)

  • Felipe Beckedorff

    (University of Miami
    University of Miami)

  • Fan Lai

    (University of Miami
    University of Miami)

  • Jingyin Yue

    (University of Miami
    University of Miami)

  • Alejandro Roisman

    (University of Miami
    University of Miami)

  • Sarah Greenblatt

    (University of Miami
    University of Miami)

  • Stephanie Duffort

    (University of Miami)

  • Lan Wang

    (University of Miami
    University of Miami
    Shanghai Jiao Tong University School of Medicine)

  • Xiaojian Sun

    (University of Miami
    University of Miami
    Shanghai Jiao Tong University School of Medicine)

  • Maria Figueroa

    (University of Miami
    University of Miami)

  • Ramin Shiekhattar

    (University of Miami
    University of Miami)

  • Stephen Nimer

    (University of Miami
    University of Miami
    University of Miami)

Abstract

AML1-ETO (AE) is a fusion transcription factor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that TATA-Box Binding Protein Associated Factor 1 (TAF1) associates with K43 acetylated AE and this association plays a pivotal role in the proliferation of AE-expressing acute myeloid leukemia (AML) cells. ChIP-sequencing indicates significant overlap of the TAF1 and AE binding sites. Knockdown of TAF1 alters the association of AE with chromatin, affecting of the expression of genes that are activated or repressed by AE. Furthermore, TAF1 is required for leukemic cell self-renewal and its reduction promotes the differentiation and apoptosis of AE+ AML cells, thereby impairing AE driven leukemogenesis. Together, our findings reveal a role of TAF1 in leukemogenesis and identify TAF1 as a potential therapeutic target for AE-expressing leukemia.

Suggested Citation

  • Ye Xu & Na Man & Daniel Karl & Concepcion Martinez & Fan Liu & Jun Sun & Camilo Jose Martinez & Gloria Mas Martin & Felipe Beckedorff & Fan Lai & Jingyin Yue & Alejandro Roisman & Sarah Greenblatt & S, 2019. "TAF1 plays a critical role in AML1-ETO driven leukemogenesis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12735-z
    DOI: 10.1038/s41467-019-12735-z
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