z-logo
open-access-imgOpen Access
Acetylation of C/EBPα inhibits its granulopoietic function
Author(s) -
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
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms10968
Subject(s) - acetylation , myeloid , ccaat enhancer binding proteins , haematopoiesis , transcription factor , biology , regulator , myelopoiesis , cell culture , microbiology and biotechnology , dna binding protein , cancer research , gene , biochemistry , genetics , stem cell
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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here
Accelerating Research

Address

John Eccles House
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom