TAF1 plays a critical role in AML1-ETO driven leukemogenesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31664040.
- Also identified by DOI 10.1038/s41467-019-12735-z and PMC identifier 6820555.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Carcinogenesis
- Core Binding Factor Alpha 2 Subunit
- Histone Acetyltransferases
- Leukemia, Myeloid, Acute
- Oncogene Proteins, Fusion
- RUNX1 Translocation Partner 1 Protein
- TATA-Binding Protein Associated Factors
- Transcription Factor TFIID