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Acetylation of C/EBPα inhibits its granulopoietic function

Author

Listed:
  • Deepak Bararia

    (Cancer Science Institute, National University of Singapore
    Dana Farber/Harvard Cancer Center
    University Hospital of the Ludwig-Maximilians-University Munich
    Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU)

  • Hui Si Kwok

    (Cancer Science Institute, National University of Singapore
    National University of Singapore Graduate School for Integrative Sciences and Engineering)

  • Robert S. Welner

    (Harvard Stem Cell Institute, Harvard Medical School
    University of Alabama at Birmingham, Birmingham)

  • Akihiko Numata

    (Cancer Science Institute, National University of Singapore)

  • Menyhárt B. Sárosi

    (Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig)

  • Henry Yang

    (Cancer Science Institute, National University of Singapore)

  • Sheena Wee

    (Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research)

  • Sebastian Tschuri

    (University Hospital of the Ludwig-Maximilians-University Munich
    Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Debleena Ray

    (Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School)

  • Oliver Weigert

    (University Hospital of the Ludwig-Maximilians-University Munich
    Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU
    German Cancer Consortium (DKTK)
    German Cancer Research Center (DKFZ))

  • Elena Levantini

    (Dana Farber/Harvard Cancer Center
    Harvard Stem Cell Institute, Harvard Medical School
    Institute of Biomedical Technologies, National Research Council (CNR))

  • Alexander K. Ebralidze

    (Dana Farber/Harvard Cancer Center
    Harvard Stem Cell Institute, Harvard Medical School)

  • Jayantha Gunaratne

    (Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Daniel G. Tenen

    (Cancer Science Institute, National University of Singapore
    Dana Farber/Harvard Cancer Center
    Harvard Stem Cell Institute, Harvard Medical School)

Abstract

CCAAT/enhancer-binding protein alpha (C/EBPα) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBPα at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBPα DNA-binding ability and modulates C/EBPα transcriptional activity. Acetylated C/EBPα is enriched in human myeloid leukaemia cell lines and acute myeloid leukaemia (AML) samples, and downregulated upon granulocyte-colony stimulating factor (G-CSF)- mediated granulocytic differentiation of 32Dcl3 cells. C/EBPα mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBPα-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBPα and demonstrate the importance of C/EBPα acetylation in myeloid differentiation.

Suggested Citation

  • Deepak Bararia & Hui Si Kwok & Robert S. Welner & Akihiko Numata & Menyhárt B. Sárosi & Henry Yang & Sheena Wee & Sebastian Tschuri & Debleena Ray & Oliver Weigert & Elena Levantini & Alexander K. Ebr, 2016. "Acetylation of C/EBPα inhibits its granulopoietic function," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10968
    DOI: 10.1038/ncomms10968
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