Pluto Bioinformatics

GSE104308 (mouse): A TFIID-SAGA perturbation that targets MYB and suppresses acute myeloid leukemia (RNA-seq)

Bulk RNA sequencing

Targeting of general coactivators, such as BRD4, is an emerging strategy to interfere with oncogenic transcription factors (TFs) in cancer. However, coactivator perturbations have the potential to influence the function of numerous TFs, thereby resulting in biological pleiotropy. Here we identify TAF12, an 18 kilodalton subunit of TFIID/SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this AML-specific dependency to a direct interaction between the TAF12/TAF4 histone-fold heterodimer and the transactivation domain of MYB, a TF with established roles in leukemogenesis. Ectopic expression of a histone-fold domain fragment of TAF4 can efficiently squelch TAF12 in cells, suppress MYB, and regress AML in mice. Our study reveals a strategy for potent MYB inhibition in AML and highlights how an oncogenic TF can be selectively neutralized by targeting a general coactivator complex. SOURCE: Yali XU (yxu@cshl.edu) - Cold Spring Harbor Laboratory