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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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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
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author 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
author_facet 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
author_sort Xu, Ye
collection PubMed
description 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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spelling pubmed-68205552019-10-31 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 Nat Commun Article 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. Nature Publishing Group UK 2019-10-29 /pmc/articles/PMC6820555/ /pubmed/31664040 http://dx.doi.org/10.1038/s41467-019-12735-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle 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
title TAF1 plays a critical role in AML1-ETO driven leukemogenesis
title_full TAF1 plays a critical role in AML1-ETO driven leukemogenesis
title_fullStr TAF1 plays a critical role in AML1-ETO driven leukemogenesis
title_full_unstemmed TAF1 plays a critical role in AML1-ETO driven leukemogenesis
title_short TAF1 plays a critical role in AML1-ETO driven leukemogenesis
title_sort taf1 plays a critical role in aml1-eto driven leukemogenesis
topic Article
url 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
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