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Blood, 1 August 2008, Vol. 112, No. 3, pp. 576-584. Prepublished online as a Blood First Edition Paper on June 3, 2008; DOI 10.1182/blood-2007-07-098996. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-07-098996v1 112/3/576    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 CrossRef Google Scholar Articles by Bouilloux, F. Articles by Morlé, F. PubMed PubMed Citation Articles by Bouilloux, F. Articles by Morlé, F. Related Collections Hematopoiesis and Stem Cells Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation Fabrice Bouilloux1,2, Gaëtan Juban1,2, Nathalie Cohet1,2, Dorothée Buet35, Boris Guyot1,2, William Vainchenker35, Fawzia Louache35, and François Morlé1,2 1 Université de Lyon, Lyon; 2 Centre National de la Recherche Scientifique (CNRS), UMR5534, Centre de Génétique Moléculaire et Cellulaire, Villeurbanne; 3 Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif; 4 Université Paris, Villejuif; and 5 Institut Gustave Roussy, Villejuif, France Previous observations suggested that functional antagonism between FLI-1 and EKLF might be involved in the commitment toward erythrocytic or megakaryocytic differentiation. We show here, using inducible shRNA expression, that EKLF knockdown in mouse erythroleukemia (MEL) cells decreases erythrocytic and increases megakaryocytic as well as Fli-1 gene expression. Chromatin immunoprecipitation analyses revealed that the increase in megakaryocytic gene expression is associated with a marked increase in RNA pol II and FLI-1 occupancy at their promoters, albeit FLI-1 protein levels are only minimally affected. Similarly, we show that human CD34+ progenitors infected with shRNA lentivirus allowing EKLF knockdown generate an increased number of differentiated megakaryocytic cells associated with increased levels of megakaryocytic and Fli-1 gene transcripts. Single-cell progeny analysis of a cell population enriched in bipotent progenitors revealed that EKLF knockdown increases the number of megakaryocytic at the expense of erythrocytic colonies. Taken together, these data indicate that EKLF restricts megakaryocytic differentiation to the benefit of erythrocytic differentiation and suggest that this might be at least partially mediated by the inhibition of FLI-1 recruitment to megakaryocytic and Fli-1 gene promoters. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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