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PMID: 9632814 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors.

Molecular and cellular biology ·Vol. 18 ·No. 7 ·1998-07-00 ·Pages 4301-14

Radomska HS, Huettner CS, Zhang P, Cheng T, Scadden DT, Tenen DG

Abstract

The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBPalpha in human granulopoiesis, we studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBPalpha initiates with the commitment of multipotential precursors to the myeloid lineage, is specifically upregulated during granulocytic differentiation, and is rapidly downregulated during the alternative monocytic pathway. Conditional expression of C/EBPalpha alone in stably transfected bipotential cells triggers neutrophilic differentiation, concomitant with upregulation of the granulocyte-specific granulocyte colony-stimulating factor receptor and secondary granule protein genes. Moreover, induced expression of C/EBPalpha in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBPalpha serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.

MeSH Terms
CCAAT-Enhancer-Binding Proteins Cell Differentiation DNA-Binding Proteins/biosynthesis,genetics Gene Expression Granulocytes/cytology HL-60 Cells HeLa Cells Hematopoietic Stem Cells/cytology Humans Lymphocytes/metabolism Macrophages/drug effects Monocytes/metabolism Nuclear Proteins/biosynthesis,genetics RNA, Messenger Tetradecanoylphorbol Acetate/pharmacology Tumor Cells, Cultured Up-Regulation
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Nuclear Proteins RNA, Messenger Tetradecanoylphorbol Acetate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Radomska H S
Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Huettner C S
Zhang P
Cheng T
Scadden D T
Tenen D G
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.7.4301
Published
1998-07-00
Pages
4301-14
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC109014
Subset
IM
Grants
NHLBI NIH HHS · HL56745 · United States
NCI NIH HHS · CA41456 · United States
NIDDK NIH HHS · DK09721 · United States
External Links
PubMed source DOI: 10.1128/MCB.18.7.4301 PMC Full Text View journal details
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