Acetylation of C/EBPα inhibits its granulopoietic function

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. Ebralidze, Jayantha Gunaratne, Daniel G. Tenen

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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.

Original languageEnglish
Article number10968
JournalNature communications
Volume7
DOIs
Publication statusPublished - Mar 23 2016

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All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Bararia, D., Kwok, H. S., Welner, R. S., Numata, A., Sárosi, M. B., Yang, H., ... Tenen, D. G. (2016). Acetylation of C/EBPα inhibits its granulopoietic function. Nature communications, 7, [10968]. https://doi.org/10.1038/ncomms10968