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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2198-2206. Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-04-019760. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-019760v1 108/7/2198    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 Pang, L. Articles by Poncz, M. Search for Related Content PubMed PubMed Citation Articles by Pang, L. Articles by Poncz, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 26, 2006 Accepted May 22, 2006 Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins Liyan Pang, Hai-Hui Xue, Gabor Szalai, Xun Wang, Yuhuan Wang, Dennis K Watson, Warren J Leonard, Gerd A Blobel*, and Mortimer Poncz Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, Bethesda, MD, USA Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, USA * Corresponding author; email: blobel{at}email.chop.edu. Numerous megakaryocyte-specific genes contain signature Ets-binding sites in their regulatory regions. Fli-1, an Ets transcription factor, is required for the normal maturation of megakaryocytes and controls the expression of multiple megakaryocyte-specific genes. However, in Fli-1-/- mice, early megakaryopoiesis persists, and the expression of the early megakaryocyte-specific genes, IIb and cMpl, is maintained, consistent with functional compensation by a related Ets factor(s). Here we identify the Ets protein GABP as a regulator of early megakaryocyte-specific genes. Notably, GABP preferentially occupies Ets elements of early megakaryocyte-specific genes in vitro and in vivo, whereas Fli-1 binds preferentially to late megakaryocyte-specific genes. Moreover, the ratio of GABP/Fli-1 expression declines throughout megakaryocyte maturation. Consistent with this expression pattern, primary fetal liver-derived megakaryocytes from Fli-1-deficient murine embryos exhibit reduced expression of genes associated with late stages of maturation (Glycoprotein (GP) Ib, GPIX and Platelet Factor 4 (PF4)), whereas GABP-deficient megakaryocytes were mostly impaired in the expression of early megakaryocyte-specific genes (IIb and cMpl). Finally, mechanistic experiments revealed that GABP, like Fli-1, can impart transcriptional synergy between the hematopoietic transcription factor GATA-1 and its cofactor FOG-1. In concert, these data reveal disparate, but overlapping, functions of Ets transcription factors at distinct stages of megakaryocyte maturation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. A. Blobel Kruppeling megakaryopoiesis Blood, December 1, 2007; 110(12): 3823 - 3824. [Full Text] [PDF] A. G. Muntean, L. Pang, M. Poncz, S. F. Dowdy, G. A. Blobel, and J. D. Crispino Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization Blood, June 15, 2007; 109(12): 5199 - 5207. [Abstract] [Full Text] [PDF]

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