A TFIID-SAGA Perturbation that Targets MYB and Suppresses Acute Myeloid Leukemia

Yali Xu, Joseph P. Milazzo, Tim D.D. Somerville, Yusuke Tarumoto, Yu Han Huang, Elizabeth L. Ostrander, John E. Wilkinson, Grant A. Challen, Christopher R. Vakoc

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Targeting of general coactivators is an emerging strategy to interfere with oncogenic transcription factors (TFs). However, coactivator perturbations often lead to pleiotropic effects by influencing numerous TFs. Here we identify TAF12, a subunit of TFIID and SAGA coactivator complexes, as a selective requirement for acute myeloid leukemia (AML) progression. We trace this 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 the TAF4 histone-fold fragment 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. Xu et al. show that TAF12 is a coactivator of MYB and protects MYB from degradation. TAF12, in a heterodimer with TAF4, interacts with the transactivation domain of MYB. Perturbation of this interaction by squelching TAF12 impairs MYB activity and leads to regression of acute myeloid leukemia in mouse models.

Original languageEnglish
Pages (from-to)13-28.e8
JournalCancer Cell
Issue number1
StatePublished - Jan 8 2018


  • MYB
  • SAGA
  • TAF12
  • acute myeloid leukemia
  • coactivator
  • epigenetics


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