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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5481-5490. Prepublished online as a Blood First Edition Paper on February 27, 2007; DOI 10.1182/blood-2006-11-060491. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-11-060491v1 109/12/5481    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 Ferreira, R. Articles by Philipsen, S. Search for Related Content PubMed PubMed Citation Articles by Ferreira, R. Articles by Philipsen, S. Related Collections Hematopoiesis and Stem Cells Red Cells Gene Expression Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Dynamic regulation of Gata factor levels is more important than their identity Rita Ferreira1, Albert Wai1, Ritsuko Shimizu2, Nynke Gillemans1, Robbert Rottier1, Marieke von Lindern3, Kinuko Ohneda3, Frank Grosveld1, Masayuki Yamamoto2, and Sjaak Philipsen1 Departments of1 Cell Biology, Erasmus MC, Rotterdam, The Netherlands; and 2 Center for Tsukuba Advanced Research Alliance and Institute of Basic Medical Sciences, University of Tsukuba, Japan; and Department of3 Hematology, Erasmus MC, Rotterdam, The Netherlands Three Gata transcription factors (Gata1, -2, and -3) are essential for hematopoiesis. These factors are thought to play distinct roles because they do not functionally replace each other. For instance, Gata2 messenger RNA (mRNA) expression is highly elevated in Gata1-null erythroid cells, yet this does not rescue the defect. Here, we test whether Gata2 and -3 transgenes rescue the erythroid defect of Gata1-null mice, if expressed in the appropriate spatiotemporal pattern. Gata1, -2, and -3 transgenes driven by ß-globin regulatory elements, directing expression to late stages of differentiation, fail to rescue erythropoiesis in Gata1-null mutants. In contrast, when controlled by Gata1 regulatory elements, directing expression to the early stages of differentiation, Gata1, -2, and -3 do rescue the Gata1-null phenotype. The dramatic increase of endogenous Gata2 mRNA in Gata1-null progenitors is not reflected in Gata2 protein levels, invoking translational regulation. Our data show that the dynamic spatiotemporal regulation of Gata factor levels is more important than their identity and provide a paradigm for developmental control mechanisms that are hard-wired in cis-regulatory elements. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: To code or not to code Anna Rita Migliaccio Blood 2007 109: 5077-5078. [Full Text] [PDF] This article has been cited by other articles: L. Gutierrez, S. Tsukamoto, M. Suzuki, H. Yamamoto-Mukai, M. Yamamoto, S. Philipsen, and K. Ohneda Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesis Blood, April 15, 2008; 111(8): 4375 - 4385. [Abstract] [Full Text] [PDF] W. T. Nottingham, A. Jarratt, M. Burgess, C. L. Speck, J.-F. Cheng, S. Prabhakar, E. M. Rubin, P.-S. Li, J. Sloane-Stanley, J. Kong-a-San, et al. Runx1-mediated hematopoietic stem-cell emergence is controlled by a Gata/Ets/SCL-regulated enhancer Blood, December 15, 2007; 110(13): 4188 - 4197. [Abstract] [Full Text] [PDF] M. Kobayashi and M. Yamamoto Regulation of GATA1 Gene Expression J. Biochem., July 1, 2007; 142(1): 1 - 10. [Abstract] [Full Text] [PDF]

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