Acetylation of C/EBPα inhibits its granulopoietic function.

Nature communications (2016-03-24)
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

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.

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MISSION® pLKO.1-puro Luciferase shRNA Control Plasmid DNA, shRNA sequence targeting luciferase