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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 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 Citation Map 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. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Human C/EBP- activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation Richa Bedi1, Jian Du1, Arun K. Sharma2, Ignatius Gomes1, and Steven J. Ackerman1 1 Department of Biochemistry and Molecular Genetics, Section of Hematology-Oncology, College of Medicine, University of Illinois at Chicago; and 2 Department of Urology and The Institute of Bionanotechnology in Medicine (IBNAM), Feinberg School of Medicine, Northwestern University, Chicago, IL CCAAT enhancer-binding protein-epsilon (C/EBP-) is required for the terminal differentiation of neutrophils and eosinophils. Human C/EBP- is expressed as 4 isoforms (32, 30, 27, and 14 kDa) through differential RNA splicing, and alternative promoters and translational start sites. The C/EBP-32/30 isoforms are transcriptional activators, whereas C/EBP-27 interacts with and represses GATA-1 transactivation of eosinophil promoters. C/EBP-14 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 internal ribosomal entry site–enhanced green fluorescent protein retroviral vectors encoding the 32/30, 27, and 14-kDa isoforms, purified by fluorescence-activated cell sorter, and analyzed in colony-forming assays and suspension cultures. Progenitors transduced with C/EBP-32/30 default exclusively to eosinophil differentiation and gene expression, independent of interleukin-5, and regardless of inclusion of cytokines to induce other lineages. In contrast, the putative repressor C/EBP-27 isoform strongly inhibits eosinophil differentiation and gene expression, including GATA-1, promoting granulocyte (neutrophil)-macrophage differen-tiation. The C/EBP-14 repressor isoform strongly inhibits eosinophil development and gene expression, promoting erythroid differentiation, an effect enhanced by erythropoietin. Thus, 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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