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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4512-4522. Prepublished online as a Blood First Edition Paper on September 19, 2008; DOI 10.1182/blood-2008-05-157560. This Article Full Text Full Text (PDF) Supplemental Figures Additional Supplemental Figures All Versions of this Article: blood-2008-05-157560v1 112/12/4512    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 Pimanda, J. E. Articles by Göttgens, B. Search for Related Content PubMed PubMed Citation Articles by Pimanda, J. E. Articles by Göttgens, B. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code John E. Pimanda1,2,*, Wan Y. I. Chan1,*, Nicola K. Wilson1, Aileen M. Smith1, Sarah Kinston1, Kathy Knezevic1,2, Mary E. Janes1,2, Josette-Renée Landry1, Anja Kolb-Kokocinski3, Jonathan Frampton4, David Tannahill3,5, Katrin Ottersbach1, George A. Follows1, Georges Lacaud6, Valerie Kouskoff6, and Berthold Göttgens1 1 Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom; 2 Lowy Cancer Research Centre and the Prince of Wales Clinical School, University of New South Wales, Sydney, Australia; 3 The Wellcome Trust Sanger Institute, Cambridge, United Kingdom; 4 Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, United Kingdom; 5 Cranfield Health, Cranfield University, Cranfield, United Kingdom; and 6 Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom Endoglin is an accessory receptor for TGF-β signaling and is required for normal hemangioblast, early hematopoietic, and vascular development. We have previously shown that an upstream enhancer, Eng –8, together with the promoter region, mediates robust endothelial expression yet is inactive in blood. To identify hematopoietic regulatory elements, we used array-based methods to determine chromatin accessibility across the entire locus. Subsequent transgenic analysis of candidate elements showed that an endothelial enhancer at Eng +9 when combined with an element at Eng +7 functions as a strong hemato-endothelial enhancer. Chromatin immunoprecipitation (ChIP)–chip analysis demonstrated specific binding of Ets factors to the promoter as well as to the –8, +7+9 enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor specific to the blood lineage, and Gata2 binding was only detected in blood. Gata2 was bound only at +7 and GATA motifs were required for hematopoietic activity. This modular assembly of regulators gives blood and endothelial cells the regulatory freedom to independently fine-tune gene expression and emphasizes the role of regulatory divergence in driving functional divergence. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-R. Landry, N. Bonadies, S. Kinston, K. Knezevic, N. K. Wilson, S. H. Oram, M. Janes, S. Piltz, M. Hammett, J. Carter, et al. Expression of the leukemia oncogene Lmo2 is controlled by an array of tissue-specific elements dispersed over 100 kb and bound by Tal1/Lmo2, Ets, and Gata factors Blood, June 4, 2009; 113(23): 5783 - 5792. [Abstract] [Full Text] [PDF]

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