MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Johansen, L. M.
Right arrow Articles by Tenen, D. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Johansen, L. M.
Right arrow Articles by Tenen, D. G.

Molecular and Cellular Biology, June 2001, p. 3789-3806, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3789-3806.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

c-Myc Is a Critical Target for C/EBPalpha in Granulopoiesis

Lisa M. Johansen,1 Atsushi Iwama,2 Tracey A. Lodie,1 Koichi Sasaki,3 Dean W. Felsher,4 Todd R. Golub,3 and Daniel G. Tenen1,*

Harvard Institutes of Medicine1 and Dana-Farber Cancer Institute,3 Harvard Medical School, Boston, Massachusetts 02115; Department of Immunology, University of Tsukuba, Tsukuba, Japan2; and Stanford University School of Medicine, Stanford, California 04305-51154

Received 6 October 2000/Returned for modification 22 November 2000/Accepted 14 March 2001

CCAAT/enhancer binding protein alpha  (C/EBPalpha ) is an integral factor in the granulocytic developmental pathway, as myeloblasts from C/EBPalpha -null mice exhibit an early block in differentiation. Since mice deficient for known C/EBPalpha target genes do not exhibit the same block in granulocyte maturation, we sought to identify additional C/EBPalpha target genes essential for myeloid cell development. To identify such genes, we used both representational difference analysis and oligonucleotide array analysis with RNA derived from a C/EBPalpha -inducible myeloid cell line. From each of these independent screens, we identified c-Myc as a C/EBPalpha negatively regulated gene. We mapped an E2F binding site in the c-Myc promoter as the cis-acting element critical for C/EBPalpha negative regulation. The identification of c-Myc as a C/EBPalpha target gene is intriguing, as it has been previously shown that down-regulation of c-Myc can induce myeloid differentiation. Here we show that stable expression of c-Myc from an exogenous promoter not responsive to C/EBPalpha -mediated down-regulation forces myeloblasts to remain in an undifferentiated state. Therefore, C/EBPalpha negative regulation of c-Myc is critical for allowing early myeloid precursors to enter a differentiation pathway. This is the first report to demonstrate that C/EBPalpha directly affects the level of c-Myc expression and, thus, the decision of myeloid blasts to enter into the granulocytic differentiation pathway.

* Corresponding author. Mailing address: Harvard Institutes of Medicine, Room 954, 77 Ave. Louis Pasteur, Boston, MA 02115. Phone: (617) 667-5561. Fax: (617) 667-3299. E-mail: dtenen{at}caregroup.harvard.edu.

Molecular and Cellular Biology, June 2001, p. 3789-3806, Vol. 21, No. 11
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.11.3789-3806.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.