Acetylation of C/EBPα inhibits its granulopoietic function
Copyright policy )Acetylation of C/EBPα inhibits its granulopoietic function
AbstractCCAAT/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.
- National University of Singapore Singapore
- National Research Council Italy
- Agency for Science, Technology and Research Singapore
- Biomedical Research Council Singapore
- Deutsche Zentren der Gesundheitsforschung Germany
570, Science, Immunoblotting, 610, Electrophoretic Mobility Shift Assay, Article, Mass Spectrometry, transcription factors, Cell Line, Tumor, Granulocyte Colony-Stimulating Factor, CCAAT-Enhancer-Binding Protein-alpha, Humans, Immunoprecipitation, p300-CBP Transcription Factors, acetylation, Myelopoiesis, Q, myeloid leukemia models, negative regulator of gene expression, Acetylation, Cell Differentiation, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, HEK293 Cells, Leukemia, Myeloid, mass spec, c/EBPa tumor suppressor transcription factor, myeloid differentiation, gene regulation, Chromatography, Liquid, Granulocytes
570, Science, Immunoblotting, 610, Electrophoretic Mobility Shift Assay, Article, Mass Spectrometry, transcription factors, Cell Line, Tumor, Granulocyte Colony-Stimulating Factor, CCAAT-Enhancer-Binding Protein-alpha, Humans, Immunoprecipitation, p300-CBP Transcription Factors, acetylation, Myelopoiesis, Q, myeloid leukemia models, negative regulator of gene expression, Acetylation, Cell Differentiation, Gene Expression Regulation, Neoplastic, Leukemia, Myeloid, Acute, HEK293 Cells, Leukemia, Myeloid, mass spec, c/EBPa tumor suppressor transcription factor, myeloid differentiation, gene regulation, Chromatography, Liquid, Granulocytes
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