title: Acetylation of C/EBPα inhibits its granulopoietic function.
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.
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.|Dana Farber/Harvard Cancer Center, Boston, Massachusetts 02215, USA.|Department of Internal Medicine III, University Hospital of the Ludwig-Maximilians-University Munich, Munich D-81377, Germany.|Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU, Munich D-81377, Germany.|German Cancer Consortium (DKTK), Heidelberg D-69120, Germany.|German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bararia
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.|National University of Singapore Graduate School for Integrative Sciences and Engineering, Singapore 117456, Singapore.
authors.forename: Hui Si
authors.initials: HS
authors.lastname: Kwok
authors.affiliation: Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.|University of Alabama at Birmingham, Department of Medicine, Division of Hematology/Oncology, Birmingham, Alabama 35294, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Welner
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Numata
authors.affiliation: Institute of Inorganic Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, Leipzig D-04103, Germany.
authors.forename: Menyhárt B
authors.initials: MB
authors.lastname: Sárosi
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.
authors.forename: Sheena
authors.initials: S
authors.lastname: Wee
authors.affiliation: Department of Internal Medicine III, University Hospital of the Ludwig-Maximilians-University Munich, Munich D-81377, Germany.|Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU, Munich D-81377, Germany.|German Cancer Consortium (DKTK), Heidelberg D-69120, Germany.|German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tschuri
authors.affiliation: Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
authors.forename: Debleena
authors.initials: D
authors.lastname: Ray
authors.affiliation: Department of Internal Medicine III, University Hospital of the Ludwig-Maximilians-University Munich, Munich D-81377, Germany.|Experimentelle Leukämie-und Lymphomforschung (ELLF), LMU, Munich D-81377, Germany.|German Cancer Consortium (DKTK), Heidelberg D-69120, Germany.|German Cancer Research Center (DKFZ), Heidelberg D-69120, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Weigert
authors.affiliation: Dana Farber/Harvard Cancer Center, Boston, Massachusetts 02215, USA.|Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.|Institute of Biomedical Technologies, National Research Council (CNR), Pisa 56124, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Levantini
authors.affiliation: Dana Farber/Harvard Cancer Center, Boston, Massachusetts 02215, USA.|Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Ebralidze
authors.affiliation: Translational Biomedical Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Singapore.|Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117594, Singapore.
authors.forename: Jayantha
authors.initials: J
authors.lastname: Gunaratne
authors.affiliation: Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.|Dana Farber/Harvard Cancer Center, Boston, Massachusetts 02215, USA.|Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D000107:Acetylation; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D013058:Mass Spectrometry; D038042:Myelopoiesis / Q000235:genetics*; D050880:p300-CBP Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D016179:Granulocyte Colony-Stimulating Factor; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor