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Blood, 1 October 2008, Vol. 112, No. 7, pp. 2738-2749. Prepublished online as a Blood First Edition Paper on July 14, 2008; DOI 10.1182/blood-2008-03-146605. This Article Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2008-03-146605v1 112/7/2738    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 Hamlett, I. Articles by Vyas, P. Search for Related Content PubMed PubMed Citation Articles by Hamlett, I. Articles by Vyas, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 25, 2008 Accepted June 9, 2008 Characterisation of megakaryocyte GATA1-interacting proteins: the co-repressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation Isla Hamlett, Julia Draper, John Strouboulis, Francisco Iborra, Catherine Porcher, and Paresh Vyas* MRC Molecular Haematology Unit and Department of Haematology, University of Oxford, Oxford, United Kingdom Institute of Molecular Oncology, BSRC Alexander Fleming, Athens, Greece * Corresponding author; email: paresh.vyas{at}imm.ox.ac.uk. The transcription factor GATA1 coordinates timely activation and repression of megakaryocyte gene expression. Loss of GATA1 function results in excessive megakaryocyte proliferation and disordered terminal platelet maturation leading to thrombocytopenia and leukaemia in patients. The mechanisms by which GATA1 does this are unclear. We have used in vivo biotinylated GATA1 to isolate megakaryocyte GATA1-partner proteins. Here, a number of independent approaches show that GATA1 interacts with several proteins in the megakaryocyte cell line L8057 and in primary megakaryocytes. They include FOG1, the NURD complex, the pentameric complex containing SCL/TAL-1, the zinc-finger regulators GFI1B and ZFP143 and the co-repressor ETO2. Knockdown of ETO2 expression promotes megakaryocyte differentiation and enhances expression of select genes expressed in terminal megakaryocyte maturation e.g. platelet factor 4 (Pf4). ETO2-dependent direct repression of the Pf4 proximal promoter is mediated by GATA-binding sites and an E-Box motif. Consistent with this, endogenous ETO2, GATA1 and the SCL pentameric complex all specifically bind the promoter in vivo. Finally, as ETO2 expression is restricted to immature megakaryocytes, these data suggest that ETO2 directly represses inappropriate early expression of a subset of terminally expressed megakaryocyte genes by binding to GATA1 and SCL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Guo, Q. Hu, C. Yan, and J. Zhang Multivalent Binding of the ETO Corepressor to E Proteins Facilitates Dual Repression Controls Targeting Chromatin and the Basal Transcription Machinery Mol. Cell. Biol., May 15, 2009; 29(10): 2644 - 2657. [Abstract] [Full Text] [PDF] D. K. Veljkovic, G. E. Rivard, M. Diamandis, J. Blavignac, E. M. Cramer-Borde, and C. P. M. Hayward Increased expression of urokinase plasminogen activator in Quebec platelet disorder is linked to megakaryocyte differentiation Blood, February 12, 2009; 113(7): 1535 - 1542. [Abstract] [Full Text] [PDF]

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