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Prepublished online as a Blood First Edition Paper on February 6, 2003; DOI 10.1182/blood-2002-09-2708. This Article Full Text (PDF) All Versions of this Article: 2002-09-2708v1 101/11/4333    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 Elagib, K. E Articles by Goldfarb, A. N Search for Related Content PubMed PubMed Citation Articles by Elagib, K. E Articles by Goldfarb, A. N Social Bookmarking                   What's this? Submitted September 4, 2002 Accepted January 23, 2003 RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation Kamaleldin E Elagib, Frederick K Racke, Michael Mogass, Rina Khetawat, Lorrie L Delehanty, and Adam N Goldfarb* Department of Pathology, University of Virginia, Charlottesville, VA, USA Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA * Corresponding author; email: ang3x{at}virginia.edu. Megakaryocytic and erythroid lineages derive from a common bipotential progenitor and share many transcription factors in common, most prominently factors of the GATA zinc finger family. Little is known about transcription factors unique to the megakaryocytic lineage that might program divergence from the erythroid pathway. To identify such factors, we employed the K562 system in which megakaryocyte lineage commitment is dependent on sustained ERK activation and is inhibited by stromal cell contact. During megakaryocytic induction in this system, the myeloid transcription factor RUNX1 underwent upregulation, dependent on ERK signaling and inhibitable by stromal cell contact. Immunostaining of normal human bone marrow confirmed strong expression of RUNX1 and cofactor CBF in megakaryocytes and minimal expression in erythroblasts. In primary human hematopoietic progenitor cultures, RUNX1 and CBF upregulation preceded megakaryocytic differentiation, and downregulation of these factors preceded erythroid differentiation. Functional studies showed cooperation among RUNX1, CBF and GATA-1 in the activation of a megakaryocytic promoter. By contrast, the RUNX1-ETO leukemic fusion protein potently repressed GATA-1 mediated transactivation. These functional interactions correlated with physical interactions observed between GATA-1 and RUNX1 factors. Enforced RUNX1 expression in K562 cells enhanced the induction of the megakaryocytic integrin proteins IIb and 2. These results suggest that RUNX1 may participate in programming of megakaryocytic lineage commitment through functional and physical interaction with GATA transcription factors. By contrast, RUNX1-ETO inhibition of GATA function may constitute a potential mechanism for the blockade of erythroid and megakaryocytic differentiation seen in leukemias with t(8;21). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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] S. Malinge, S. Izraeli, and J. D. Crispino Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome Blood, March 19, 2009; 113(12): 2619 - 2628. [Abstract] [Full Text] [PDF] O. 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