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.
Keywords: AMLs; BRPF; C-terminal domain of the RNA-polymerase II; CPSF100; CTD-RNA-PolII; EAF6; Esa1-associated factor 6 ortholog; HAT; HMT; HOX; HOXA9; HSF1; ING5; MLL; MOZ; MOZ/YBF2/SAS2/TIP60 homology domain; MYST; PHD; RUNX1; Spi-1/PU.1; Symplekin; Transcription regulation; acute myeloid leukemias; bromodomain and PHD finger-containing protein; cleavage and polyadenylation specificity factor 100; heat shock factor 1; histone acetyltransferase; histone methyltransferase; homeobox; inhibitor of growth 5; mixed lineage leukemia; monocytic leukemia zinc finger; plant homeodomain; runt-related transcription factor 1; spleen focus forming virus proviral integration oncogene/purine-rich box-1.
© 2013.