TAF1 plays a critical role in AML1-ETO driven leukemogenesis.

Abstract:

: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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Xu Y,Man N,Karl D,Martinez C,Liu F,Sun J,Martinez CJ,Martin GM,Beckedorff F,Lai F,Yue J,Roisman A,Greenblatt S,Duffort S,Wang L,Sun X,Figueroa M,Shiekhattar R,Nimer S

doi

10.1038/s41467-019-12735-z

subject

Has Abstract

pub_date

2019-10-29 00:00:00

pages

4925

issue

1

issn

2041-1723

pii

10.1038/s41467-019-12735-z

journal_volume

10

pub_type

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