Acetylation of C/EBP? inhibits its granulopoietic function.

ABSTRACT: CCAAT/enhancer-binding protein alpha (C/EBP?) is an essential transcription factor for myeloid lineage commitment. Here we demonstrate that acetylation of C/EBP? at lysine residues K298 and K302, mediated at least in part by general control non-derepressible 5 (GCN5), impairs C/EBP? DNA-binding ability and modulates C/EBP? transcriptional activity. Acetylated C/EBP? 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/EBP? mutants that mimic acetylation failed to induce granulocytic differentiation in C/EBP?-dependent assays, in both cell lines and in primary hematopoietic cells. Our data uncover GCN5 as a negative regulator of C/EBP? and demonstrate the importance of C/EBP? acetylation in myeloid differentiation.

SUBMITTER: Bararia D 

PROVIDER: S-EPMC4814574 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature