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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 pr...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820555/
https://www.ncbi.nlm.nih.gov/pubmed/31664040
http://dx.doi.org/10.1038/s41467-019-12735-z
Descripción
Sumario: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.