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

doi:10.1038/s41467-019-12735-z

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 journal › Article

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 language	English (US)
Article number	4925
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12735-z
State	Published - Dec 1 2019

ASJC Scopus subject areas

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

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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

TAF1 plays a critical role in AML1-ETO driven leukemogenesis. / Xu, Ye; Man, Na; Karl, Daniel; Martinez, Concepcion; Liu, Fan; Sun, Jun; Martinez, Camilo Jose; Martin, Gloria Mas; Beckedorff, Felipe; Lai, Fan; Yue, Jingyin; Roisman, Alejandro; Greenblatt, Sarah; Duffort, Stephanie; Wang, Lan; Sun, Xiaojian; Figueroa, Maria ; Shiekhattar, Ramin ; Nimer, Stephen.

In: Nature communications, Vol. 10, No. 1, 4925, 01.12.2019.

Research output: Contribution to journal › Article

Xu, Ye ; Man, Na ; Karl, Daniel ; Martinez, Concepcion ; Liu, Fan ; Sun, Jun ; Martinez, Camilo Jose ; Martin, Gloria Mas ; Beckedorff, Felipe ; Lai, Fan ; Yue, Jingyin ; Roisman, Alejandro ; Greenblatt, Sarah ; Duffort, Stephanie ; Wang, Lan ; Sun, Xiaojian ; Figueroa, Maria ; Shiekhattar, Ramin ; Nimer, Stephen. / TAF1 plays a critical role in AML1-ETO driven leukemogenesis. In: Nature communications. 2019 ; Vol. 10, No. 1.

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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.",

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AU - Man, Na

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AU - Sun, Jun

AU - Martinez, Camilo Jose

AU - Martin, Gloria Mas

AU - Beckedorff, Felipe

AU - Lai, Fan

AU - Yue, Jingyin

AU - Roisman, Alejandro

AU - Greenblatt, Sarah

AU - Duffort, Stephanie

AU - Wang, Lan

AU - Sun, Xiaojian

AU - Figueroa, Maria

AU - Shiekhattar, Ramin

AU - Nimer, Stephen

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N2 - 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.

AB - 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.

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