TAF1 plays a critical role in AML1-ETO driven leukemogenesis.

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.

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, Stephanie Duffort, Lan Wang, Xiaojian Sun, Maria Figueroa, Ramin Shiekhattar, Stephen Nimer. TAF1 plays a critical role in AML1-ETO driven leukemogenesis. Nature communications. 2019 Oct 29;10(1):4925

Mesh Tags

Substances

PMID: 31664040

search → result