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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1251-1259. Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-02-001461. This Article Full Text (PDF) Supplemental Table and Figure All Versions of this Article: blood-2006-02-001461v1 108/4/1251    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 Mollica, L. R Articles by Lane, D. A Search for Related Content PubMed PubMed Citation Articles by Mollica, L. R Articles by Lane, D. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 2, 2006 Accepted April 3, 2006 Role of a 5' -enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene Luigina R Mollica, James T.B. Crawley*, Ke Liu, James B Rance, Peter N Cockerill, George A Follows, Josette-Renee Landry, Dominic J Wells, and David A Lane Department of Haematology, Imperial College London, London, UK Department of Cellular & Molecular Neuroscience, Imperial College London, London, UK Experimental Haematology, Leeds Institute of Molecular Medicine, University of Leeds, UK Department of Haematology, University of Cambridge, Cambridge, UK * Corresponding author; email: j.crawley{at}imperial.ac.uk. The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by haematopoietic stem cells. DNaseI hypersensitive (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified three potential regulatory elements. By itself, the DH region spanning the proximal promoter (PP) was unable to direct cell-specific transcription in transgenic mice. A second DH element, located upstream of PP and termed -5.5HS, was hypersensitive only in EC and immature haematopoietic cell lines. Transgenes expressing LacZ under the control of -5.5HS coupled to either PP or the SV40 promoter were able to direct -galactosidase activity to the endothelium of large vessels during embryogenesis and adulthood. The -5.5HS exhibited enhancer activity that was conferred by the interplay of transcription factors interacting with conserved Ets and composite GATA/Tal1 motifs. The third DH element, located in intron 2, was primarily hypersensitive in EPCR-negative cells, and capable of initiating antisense transcription, suggesting a role in hEPCR silencing. This study identifies critical elements required for the tissue-specificity of hEPCR, and suggests a mechanism for endothelial and haematopoietic stem cell-specific transcriptional regulation that reflects the common origin of these cell types. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Ogilvy, R. Ferreira, S. G. Piltz, J. M. Bowen, B. Gottgens, and A. R. Green The SCL +40 Enhancer Targets the Midbrain Together with Primitive and Definitive Hematopoiesis and Is Regulated by SCL and GATA Proteins Mol. Cell. Biol., October 15, 2007; 27(20): 7206 - 7219. [Abstract] [Full Text] [PDF] L. O. Mosnier, B. V. Zlokovic, and J. H. Griffin The cytoprotective protein C pathway Blood, April 15, 2007; 109(8): 3161 - 3172. [Abstract] [Full Text] [PDF] M. Thiyagarajan, T. Cheng, and B. V. Zlokovic Endothelial Cell Protein C Receptor: Role Beyond Endothelium? Circ. Res., February 2, 2007; 100(2): 155 - 157. [Full Text] [PDF]

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