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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2248-2256. Prepublished online as a Blood First Edition Paper on June 8, 2006; DOI 10.1182/blood-2006-02-002188. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-002188v1 108/7/2248    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 McCormack, M. P. Articles by Curtis, D. J. Search for Related Content PubMed PubMed Citation Articles by McCormack, M. P. Articles by Curtis, D. J. Related Collections Gene Expression Hematopoiesis Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis Matthew P. McCormack, Mark A. Hall, Simone M. Schoenwaelder, Quan Zhao, Sarah Ellis, Julia A. Prentice, Ashleigh J. Clarke, Nicholas J. Slater, Jessica M. Salmon, Shaun P. Jackson, Stephen M. Jane, and David J. Curtis From the Bone Marrow Research Laboratories, Royal Melbourne Hospital, Melbourne Health Research Directorate, c/o Royal Melbourne Hospital Post Office, Parkville; the Australian Centre for Blood Diseases, Monash University, Alfred Medical Research Education Precinct, Melbourne; the Microscopy Imaging Facility, Peter MacCallum Research Institute, East Melbourne, Victoria; and the Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Australia. The generation of platelets from megakaryocytes in the steady state is regulated by a variety of cytokines and transcription factors, including thrombopoietin (TPO), GATA-1, and NF-E2. Less is known about platelet production in the setting of stress thrombopoiesis, a pivotal event in the context of cytotoxic chemotherapy. Here we show in mice that the transcription factor Scl is critical for platelet production after chemotherapy and in thrombopoiesis induced by administration of TPO. Megakaryocytes from these mice showed appropriate increases in number and ploidy but failed to shed platelets. Ultrastructural examination of Scl-null megakaryocytes revealed a disorganized demarcation membrane and reduction in platelet granules. Quantitative real-time polymerase chain reaction showed that Scl-null platelets lacked NF-E2, and chromatin immunoprecipitation analysis demonstrated Scl binding to the NF-E2 promoter in the human megakaryoblastic-cell line Meg-01, along with its binding partners E47, Lmo2, and the cofactors Ldb1 and GATA-2. These findings suggest that Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. M. Salmon, N. J. Slater, M. A. Hall, M. P. McCormack, S. L. Nutt, S. M. Jane, and D. J. Curtis Aberrant mast-cell differentiation in mice lacking the stem-cell leukemia gene Blood, November 15, 2007; 110(10): 3573 - 3581. [Abstract] [Full Text] [PDF] V. Deleuze, E. Chalhoub, R. El-Hajj, C. Dohet, M. Le Clech, P.-O. Couraud, P. Huber, and D. Mathieu TAL-1/SCL and Its Partners E47 and LMO2 Up-Regulate VE-Cadherin Expression in Endothelial Cells Mol. Cell. Biol., April 1, 2007; 27(7): 2687 - 2697. [Abstract] [Full Text] [PDF]

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