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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1223-1231. Prepublished online as a Blood First Edition Paper on April 28, 2005; DOI 10.1182/blood-2005-02-0551. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-02-0551v1 106/4/1223    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 Muntean, A. G. Articles by Crispino, J. D. Search for Related Content PubMed PubMed Citation Articles by Muntean, A. G. Articles by Crispino, J. D. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Differential requirements for the activation domain and FOG-interaction surface of GATA-1 in megakaryocyte gene expression and development Andrew G. Muntean, and John D. Crispino From the Ben May Institute for Cancer Research, University of Chicago, Chicago, IL. GATA1 is mutated in patients with 2 different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and thrombocytopenia. Second, children with Down syndrome who develop acute megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive expression of a shorter isoform named GATA-1s. To determine the effect of these patient-specific mutations on GATA-1 function, we first compared the gene expression profile between wild-type and GATA-1–deficient megakaryocytes. Next, we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1–deficient megakaryocytes and assessed the effect on differentiation and gene expression. Whereas GATA-1–deficient megakaryocytes failed to undergo terminal differentiation and proliferated excessively in vitro, GATA-1s–expressing cells displayed proplatelet formation and other features of terminal maturation, but continued to proliferate aberrantly. In contrast, megakaryocytes that expressed V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation. Examination of the expression of megakaryocyte-specific genes in the various rescued cells correlated with the observed phenotypic differences. These studies show that GATA-1 is required for both normal regulation of proliferation and terminal maturation of megakaryocytes, and further, that these functions can be uncoupled by mutations in GATA1. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. A. Steiner, Y. Maksimova, V. Schulz, C. Wong, D. Raha, M. C. Mahajan, S. M. Weissman, and P. G. Gallagher Chromatin Architecture and Transcription Factor Binding Regulate Expression of Erythrocyte Membrane Protein Genes Mol. Cell. Biol., October 15, 2009; 29(20): 5399 - 5412. [Abstract] [Full Text] [PDF] Z. Huang, L. C. Dore, Z. Li, S. H. Orkin, G. Feng, S. Lin, and J. D. Crispino GATA-2 Reinforces Megakaryocyte Development in the Absence of GATA-1 Mol. Cell. Biol., September 15, 2009; 29(18): 5168 - 5180. [Abstract] [Full Text] [PDF] C. Niu, J. Zhang, P. Breslin, M. Onciu, Z. Ma, and S. W. 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