Symplekin, a polyadenylation factor, prevents MOZ and MLL activity on HOXA9 in hematopoietic cells

Anne Largeot, Jérôme Paggetti, Julien Broséus, Romain Aucagne, Brice Lagrange, Romain Z. Martin, Jean Berthelet, Ronan Quéré, Géraldine Lucchi, Patrick Ducoroy, Jean Noël Bastie, Laurent Delva*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    2 Citations (Scopus)

    Abstract

    MOZ and MLL encoding a histone acetyltransferase and a histone methyltransferase, respectively, are targets for recurrent chromosomal translocations found in acute myeloblastic or lymphoblastic leukemia. We have previously shown that MOZ and MLL cooperate to activate HOXA9 gene expression in hematopoietic stem/progenitors cells. To dissect the mechanism of action of this complex, we decided to identify new proteins interacting with MOZ. We found that the scaffold protein Symplekin that supports the assembly of polyadenylation machinery was identified by mass spectrometry. Symplekin interacts and co-localizes with both MOZ and MLL in immature hematopoietic cells. Its inhibition leads to a decrease of the HOXA9 protein level but not of Hoxa9 mRNA and to an over-recruitment of MOZ and MLL onto the HOXA9 promoter. Altogether, our results highlight the role of Symplekin in transcription repression involving a regulatory network between MOZ, MLL and Symplekin.

    Original languageEnglish
    Pages (from-to)3054-3063
    Number of pages10
    JournalBiochimica et Biophysica Acta - Molecular Cell Research
    Volume1833
    Issue number12
    DOIs
    Publication statusPublished - Dec 2013

    Keywords

    • HOXA9
    • MLL
    • MOZ
    • Symplekin
    • Transcription regulation

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