Acetylation of C/EBPα inhibits its granulopoietic function

• Published in: Nature communications 2016-03, Vol.7 (1), p.10968-10968, Article 10968
• Main Authors: Bararia, Deepak, Kwok, Hui Si, Welner, Robert S., Numata, Akihiko, Sárosi, Menyhárt B., Yang, Henry, Wee, Sheena, Tschuri, Sebastian, Ray, Debleena, Weigert, Oliver, Levantini, Elena, Ebralidze, Alexander K., Gunaratne, Jayantha, Tenen, Daniel G.
• Format: Article
• Language: English
• Subjects: 13/1; 13/100; 13/109; 13/31; 13/44; 631/250/232; 631/337/458/1275; 631/45/612/822; 631/67/1990/283; 64/60; 82/58; 82/80; 82/83; Acetylation; CCAAT-Enhancer-Binding Protein-alpha - metabolism; Cell Differentiation - genetics; Cell Line, Tumor; Chromatography, Liquid; Electrophoretic Mobility Shift Assay; Gene Expression Regulation, Neoplastic; Granulocyte Colony-Stimulating Factor; Granulocytes - cytology; Granulocytes - metabolism; HEK293 Cells; Humanities and Social Sciences; Humans; Immunoblotting; Immunoprecipitation; Leukemia, Myeloid - genetics; Leukemia, Myeloid - metabolism; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Mass Spectrometry; multidisciplinary; Myelopoiesis - genetics; p300-CBP Transcription Factors - genetics; p300-CBP Transcription Factors - metabolism; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10968

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. C/EBPα is an essential transcription factor for myeloid lineage commitment. Here, the authors show that acetylation of C/EBPα at K298 and K302, mediated at least in part by GCN5, impairs C/EBPα DNA binding ability and modulates C/EBPα transcriptional activity.