TAF1 plays a critical role in AML1-ETO driven leukemogenesis
2019
AML1-ETO (AE) is a
fusion transcriptionfactor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that
TATA-BoxBinding 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-sequencingindicates significant overlap of the
TAF1and AE binding sites. Knockdown of
TAF1alters the association of AE with chromatin, affecting of the expression of genes that are activated or repressed by AE. Furthermore,
TAF1is 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
TAF1in leukemogenesis and identify
TAF1as 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
TAF1is 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.
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