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Blood, 8 January 2009, Vol. 113, No. 2, pp. 317-327. Prepublished online as a Blood First Edition Paper on October 2, 2008; DOI 10.1182/blood-2008-02-139741. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-02-139741v1 113/2/317    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bedi, R. Articles by Ackerman, S. J. Search for Related Content PubMed PubMed Citation Articles by Bedi, R. Articles by Ackerman, S. J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2008 Accepted September 8, 2008 Human C/EBP activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation Richa Bedi, Jian Du, Arun K. Sharma, Ignatius Gomes, and Steven J. Ackerman* Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, United States Department of Urology, and the Institute of Bionanotechnology in Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States * Corresponding author; email: sackerma{at}uic.edu. CCAAT enhancer binding protein epsilon (C/EBP) is required for the terminal differentiation of neutrophils and eosinophils. Human C/EBP is expressed as four isoforms (32, 30, 27 and 14kD) through differential RNA splicing, and alternative promoters and translational start sites. The C/EBP32/30 isoforms are transcriptional activators, whereas C/EBP27 interacts with and represses GATA-1 transactivation of eosinophil promoters. C/EBP14 contains only DNA binding and dimerization domains, and may function as a dominant negative regulator. To define functional activities for these C/EBP isoforms in myelopoiesis, human CD34+ progenitors were transduced with IRES-eGFP retroviral vectors encoding the 32/30, 27 and 14kD isoforms, purified by FACS, and analyzed in colony-forming assays and suspension cultures. Progenitors transduced with C/EBP32/30 default exclusively to eosinophil differentiation and gene expression, independent of IL-5, and regardless of inclusion of cytokines to induce other lineages. In contrast, the putative repressor C/EBP27 isoform strongly inhibits eosinophil differentiation and gene expression, including GATA-1, promoting granulocyte (neutrophil)-macrophage differentiation. The C/EBP14 repressor isoform strongly inhibits eosinophil development and gene expression, promoting erythroid differentiation, an effect enhanced by erythropoietin. Thus, the C/EBP isoforms can reprogram myeloid lineage commitment and differentiation consistent with their predicted activities based on activator and repressor domains and in vitro functional activities. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Z. Qiu, K. D. Dyer, Z. Xie, M. Radinger, and H. F. Rosenberg GATA Transcription Factors Regulate the Expression of the Human Eosinophil-derived Neurotoxin (RNase 2) Gene J. Biol. Chem., May 8, 2009; 284(19): 13099 - 13109. [Abstract] [Full Text] [PDF]

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