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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 8, 2005 Accepted April 12, 2005 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* Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, USA * Corresponding author; email: crispino{at}huggins.bsd.uchicago.edu. GATA1 is mutated in patients with two different disorders. First, individuals with a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor 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. While 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: A. J. Woo, T. B. Moran, Y. L. Schindler, S.-K. Choe, N. B. Langer, M. R. Sullivan, Y. Fujiwara, B. H. Paw, and A. B. Cantor Identification of ZBP-89 as a Novel GATA-1-Associated Transcription Factor Involved in Megakaryocytic and Erythroid Development Mol. Cell. Biol., April 15, 2008; 28(8): 2675 - 2689. [Abstract] [Full Text] [PDF] D. Webb, I. Roberts, and P. Vyas Haematology of Down syndrome Arch. Dis. Child. Fetal Neonatal Ed., November 1, 2007; 92(6): F503 - F507. [Abstract] [Full Text] [PDF] S.-I. Kim, S. J. Bultman, H. Jing, G. A. Blobel, and E. H. 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