Acetylation of C/EBPα inhibits its granulopoietic function

Nat Commun. 2016 Mar 23:7:10968. doi: 10.1038/ncomms10968.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Mass Spectrometry
  • Myelopoiesis / genetics*
  • p300-CBP Transcription Factors / genetics*
  • p300-CBP Transcription Factors / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-alpha
  • Granulocyte Colony-Stimulating Factor
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor