TY - JOUR
T1 - TAF1 plays a critical role in AML1-ETO driven leukemogenesis
AU - Xu, Ye
AU - Man, Na
AU - Karl, Daniel
AU - Martinez, Concepcion
AU - Liu, Fan
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
N1 - Funding Information:
We thank the members of Dr. Nimer’s lab for their technical support and helpful suggestions and Delphine Prou for her assistance in animal study. We also thank Bernard Jay Wasserlauf for his technical support on IVIS, the Flow Cytometry Shared Resources for sorting and flow cytometry analysis, Oncogenomic Shared Resources and Bioinfor-matics and Biostatistics Shared Resources at Sylvester Comprehensive Cancer Center for RNA-sequencing and ChIP-sequencing library preparation and sequencing. We also thank Dr. Stefan Kubicek at CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences in Australia, Dr. Hartmut Geiger at Ulm University in Germany, and Dr. Bob Roeder at Rockefeller University for generously providing TAF1 antibodies. Alejandro Roisman is a Fellow of The Leukemia & Lymphoma Society. This project was supported by a grant from National Cancer Institute (R01CA166835) to S.N. and a grant from American Cancer Society (IRG-17-183-16) to Y.X.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
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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U2 - 10.1038/s41467-019-12735-z
DO - 10.1038/s41467-019-12735-z
M3 - Article
C2 - 31664040
AN - SCOPUS:85074273808
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4925
ER -