TAF1 plays a critical role in AML1-ETO driven leukemogenesis

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, Stephanie Duffort, Lan Wang, Xiaojian Sun, Maria Figueroa, Ramin Shiekhattar, Stephen Nimer

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number4925
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'TAF1 plays a critical role in AML1-ETO driven leukemogenesis'. Together they form a unique fingerprint.

  • Cite this

    Xu, Y., Man, N., Karl, D., Martinez, C., Liu, F., Sun, J., Martinez, C. J., Martin, G. M., Beckedorff, F., Lai, F., Yue, J., Roisman, A., Greenblatt, S., Duffort, S., Wang, L., Sun, X., Figueroa, M., Shiekhattar, R., & Nimer, S. (2019). TAF1 plays a critical role in AML1-ETO driven leukemogenesis. Nature communications, 10(1), [4925]. https://doi.org/10.1038/s41467-019-12735-z