TAF1 plays a critical role in AML1-ETO driven leukemogenesis
| Autor: | Stephen D. Nimer, Xiao-Jian Sun, Lan Wang, Alejandro Roisman, Fan Liu, Fan Lai, Concepción Martínez, Gloria Mas Martin, Ramin Shiekhattar, Jingyin Yue, Felipe Beckedorff, Jun Sun, Ye Xu, Maria E. Figueroa, Sarah Greenblatt, Na Man, Daniel L. Karl, Camilo Martinez, Stephanie Duffort |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncogene Proteins Fusion Carcinogenesis Cellular differentiation General Physics and Astronomy RUNX1 Translocation Partner 1 Protein 0302 clinical medicine hemic and lymphatic diseases Myeloid Cells Cell Self Renewal lcsh:Science Histone Acetyltransferases Gene knockdown Multidisciplinary Gene Expression Regulation Leukemic Chemistry Myeloid leukemia Acetylation Cell Differentiation Chromatin Cell biology Leukemia Myeloid Acute TAF1 Leukemia 030220 oncology & carcinogenesis Core Binding Factor Alpha 2 Subunit Protein Binding Science Article Acute myeloid leukaemia General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Protein Domains Cell Line Tumor medicine Animals Humans neoplasms Transcription factor Cell Proliferation TATA-Binding Protein Associated Factors Oncogene Lysine General Chemistry medicine.disease Mice Inbred C57BL 030104 developmental biology lcsh:Q Transcription Factor TFIID |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-15 (2019) |
| ISSN: | 2041-1723 |
| Popis: | 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. AML1-ETO is a fusion protein in which acetylation of lysine-43 is critical to leukemogenesis. Here, they show that TAF1 is required for AML1-ETO mediated gene expression such that it binds to acetylated AML1-ETO to facilitate the association of AML1-ETO with chromatin, and consequently, promotes leukemic self-renewal. |
| Databáze: | OpenAIRE |
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