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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-05-1546. This Article Full Text (PDF) All Versions of this Article: 2002-05-1546v1 101/6/2206    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 Cammenga, J. Articles by Nimer, S. D Search for Related Content PubMed PubMed Citation Articles by Cammenga, J. Articles by Nimer, S. D Social Bookmarking                   What's this? Submitted June 4, 2002 Accepted October 16, 2002 Induction of C/EBP activity alters gene expression and differentiation of human CD34+ cells Jorg Cammenga, James C Mulloy, Francisco J Berguido, Donal MacGrogan, Agnes Viale, and Stephen D Nimer* Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute, New York, NY, USA Genomics Core Laboratory, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute, New York, NY, USA * Corresponding author; email: s-nimer{at}mskcc.org. The CCAAT/enhancer binding protein alpha (C/EBP) belongs to a family of transcription factors that are involved in the differentiation process of numerous tissues, including the liver and hematopoietic cells. C/EBP -/- mice show a block in hematopoietic differentiation, with an accumulation of myeloblasts and an absence of mature granulocytes, whereas expression of C/EBP in leukemia cell lines leads to granulocytic differentiation. Recently, dominant negative mutations in the C/EBP gene and down-regulation of C/EBP by AML1-ETO, an AML associated fusion protein, have been identified in acute myelogenous leukemia (AML). To better understand the role of C/EBP in the lineage commitment and differentiation of hematopoietic progenitors, we transduced primary human CD34+ cells with a retroviral construct that expresses the C/EBP cDNA fused in-frame with the estrogen receptor ligand-binding domain. Induction of C/EBP function in primary human CD34+ cells, by the addition of ß-estradiol, leads to granulocytic differentiation and inhibits erythrocyte differentiation. Using Affymetrix oligonucleotide arrays we have identified C/EBP target genes in primary human hematopoietic cells, including granulocyte specific genes that are involved in hematopoietic differentiation and Id1, a transcriptional repressor known to interfere with erythrocyte differentiation. Given the known differences in murine and human promoter regulatory sequences, this inducible system allows the identification of transcription factor target genes in a physiological, human hematopoietic progenitor cell background. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kandilci and G. C. Grosveld Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyperproliferation and restores myeloid differentiation Blood, August 20, 2009; 114(8): 1596 - 1606. [Abstract] [Full Text] [PDF] G. Marcucci, K. Maharry, M. D. Radmacher, K. Mrozek, T. Vukosavljevic, P. Paschka, S. P. 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