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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 (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 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 Bouilloux, F. Articles by Morle, F. Search for Related Content PubMed PubMed Citation Articles by Bouilloux, F. Articles by Morle, F. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 2, 2007 Accepted May 11, 2008 EKLF restricts megakaryocytic differentiation at the benefit of erythrocytic differentiation Fabrice Bouilloux, Gaetan Juban, Nathalie Cohet, Dorothee Buet, Boris Guyot, William Vainchenker, Fawzia Louache, and Francois Morle* CNRS, UMR5534, Centre de Genetique Moleculaire et Cellulaire, CNRS, Universite Lyon1, Villeurbanne, France INSERM, UMR790, INSERM, Universite Paris XI, Institut Gustave Roussy, Villejuif, France * Corresponding author; email: morle{at}univ-lyon1.fr. 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 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 at 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? This article has been cited by other articles: Y. Guo, C. Niu, P. Breslin, M. Tang, S. Zhang, W. Wei, A. R. Kini, G. P. Paner, S. Alkan, S. W. Morris, et al. c-Myc-mediated control of cell fate in megakaryocyte-erythrocyte progenitors Blood, September 3, 2009; 114(10): 2097 - 2106. [Abstract] [Full Text] [PDF] O. Klimchenko, M. Mori, A. DiStefano, T. Langlois, F. Larbret, Y. Lecluse, O. Feraud, W. Vainchenker, F. Norol, and N. Debili A common bipotent progenitor generates the erythroid and megakaryocyte lineages in embryonic stem cell-derived primitive hematopoiesis Blood, August 20, 2009; 114(8): 1506 - 1517. [Abstract] [Full Text] [PDF] H. Huang, M. Yu, T. E. Akie, T. B. Moran, A. J. Woo, N. Tu, Z. Waldon, Y. Y. Lin, H. Steen, and A. B. Cantor Differentiation-Dependent Interactions between RUNX-1 and FLI-1 during Megakaryocyte Development Mol. Cell. Biol., August 1, 2009; 29(15): 4103 - 4115. [Abstract] [Full Text] [PDF] M. R. Tallack, J. R. Keys, P. O. Humbert, and A. C. Perkins EKLF/KLF1 Controls Cell Cycle Entry via Direct Regulation of E2f2 J. Biol. Chem., July 31, 2009; 284(31): 20966 - 20974. [Abstract] [Full Text] [PDF] M. J. Stankiewicz and J. D. Crispino ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells Blood, April 2, 2009; 113(14): 3337 - 3347. [Abstract] [Full Text] [PDF] T. Sengupta, N. Cohet, F. Morle, and J. J. Bieker Distinct modes of gene regulation by a cell-specific transcriptional activator PNAS, March 17, 2009; 106(11): 4213 - 4218. [Abstract] [Full Text] [PDF] D. K. Veljkovic, G. E. Rivard, M. Diamandis, J. Blavignac, E. M. Cramer-Borde, and C. P. M. Hayward Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation Blood, February 12, 2009; 113(7): 1535 - 1542. [Abstract] [Full Text] [PDF] T. Sengupta, K. Chen, E. Milot, and J. J. Bieker Acetylation of EKLF Is Essential for Epigenetic Modification and Transcriptional Activation of the {beta}-Globin Locus Mol. Cell. Biol., October 15, 2008; 28(20): 6160 - 6170. [Abstract] [Full Text] [PDF]

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