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Publication : Acetylation of C/EBPα inhibits its granulopoietic function.

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.
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