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AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription

Author

Listed:
  • Hiroshi Okuda

    (Laboratory for Malignancy Control Research, Kyoto University Graduate School of Medicine)

  • Akinori Kanai

    (Research Institute for Radiation Biology and Medicine, Hiroshima University)

  • Shinji Ito

    (Medical Research Support Center, Kyoto University Graduate School of Medicine)

  • Hirotaka Matsui

    (Research Institute for Radiation Biology and Medicine, Hiroshima University
    Present address: Department of Molecular Laboratory Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan)

  • Akihiko Yokoyama

    (Laboratory for Malignancy Control Research, Kyoto University Graduate School of Medicine)

Abstract

Gene rearrangements generate MLL fusion genes, which can lead to aggressive leukemia. In most cases, MLL fuses with a gene encoding a component of the AEP (AF4 family/ENL family/P-TEFb) coactivator complex. MLL–AEP fusion proteins constitutively activate their target genes to immortalize haematopoietic progenitors. Here we show that AEP and MLL–AEP fusion proteins activate transcription through selectivity factor 1 (SL1), a core component of the pre-initiation complex (PIC) of RNA polymerase I (RNAP1). The pSER domain of AF4 family proteins associates with SL1 on chromatin and loads TATA-binding protein (TBP) onto the promoter to initiate RNA polymerase II (RNAP2)-dependent transcription. These results reveal a previously unknown transcription initiation mechanism involving AEP and a role for SL1 as a TBP-loading factor in RNAP2-dependent gene activation.

Suggested Citation

  • Hiroshi Okuda & Akinori Kanai & Shinji Ito & Hirotaka Matsui & Akihiko Yokoyama, 2015. "AF4 uses the SL1 components of RNAP1 machinery to initiate MLL fusion- and AEP-dependent transcription," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9869
    DOI: 10.1038/ncomms9869
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