First Author | Bararia D | Year | 2016 |
Journal | Nat Commun | Volume | 7 |
Pages | 10968 | PubMed ID | 27005833 |
Mgi Jnum | J:236743 | Mgi Id | MGI:5807013 |
Doi | 10.1038/ncomms10968 | Citation | Bararia D, et al. (2016) Acetylation of C/EBPalpha inhibits its granulopoietic function. Nat Commun 7:10968 |
abstractText | CCAAT/enhancer-binding protein alpha (C/EBPalpha) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBPalpha at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBPalpha DNA-binding ability and modulates C/EBPalpha transcriptional activity. Acetylated C/EBPalpha 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/EBPalpha mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBPalpha-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBPalpha and demonstrate the importance of C/EBPalpha acetylation in myeloid differentiation. |