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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1531-1539. Prepublished online as a Blood First Edition Paper on October 21, 2004; DOI 10.1182/blood-2002-10-3093. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3093v1 105/4/1531    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 Hough, C. Articles by Lillicrap, D. Search for Related Content PubMed PubMed Citation Articles by Hough, C. Articles by Lillicrap, D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Cell type–specific regulation of von Willebrand factor expression by the E4BP4 transcriptional repressor Christine Hough, Carla D. Cuthbert, Colleen Notley, Christine Brown, Carol Hegadorn, Ergul Berber, and David Lillicrap From The Department of Pathology and Molecular Medicine, Richardson Laboratories, Queen's University, Kingston, ON. Mechanisms of tissue-restricted patterns of von Willebrand factor (VWF) expression involve activators and repressors that limit expression to endothelial cells and megakaryocytes. The relative transcriptional activity of the proximal VWF promoter was assessed in VWF-producing and -nonproducing cells, and promoter activity was highest in endothelial cells followed by megakaryocytes. Only basal VWF promoter activity was seen in nonendothelial cells. Here we identify a negative response element located at nucleotides (nts) +96/+105 and demonstrate, using chromatin immunoprecipitation (ChIP) analysis, that in vivo this sequence interacts with the E4BP4 transcriptional repressor. Differences in size and relative abundance of nuclear E4BP4 were observed. In HepG2 cells, low levels of larger forms of E4BP4 are present that directly interact with the negative response element. In VWF-expressing cells, high levels of smaller forms predominate with no evidence of direct DNA binding. However, in endothelial cells, mutation of the VWF E4BP4 binding motif not only restores but also further elevates VWF promoter activity, suggesting that E4BP4 may be part of a coordinated binding complex. These observations implicate this binding motif in repressing both activated and basal levels of VWF transcription by different cell type–specific mechanisms, and support the hypothesis that E4BP4 sequesters negative regulators of transcription, thereby enhancing activated gene expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Nishikawa, K. Hagihara, S. Serada, T. Isobe, A. Matsumura, J. Song, T. Tanaka, I. Kawase, T. Naka, and K. Yoshizaki Transcriptional Complex Formation of c-Fos, STAT3, and Hepatocyte NF-1{alpha} Is Essential for Cytokine-Driven C-Reactive Protein Gene Expression J. Immunol., March 1, 2008; 180(5): 3492 - 3501. [Abstract] [Full Text] [PDF] A. M. Kleinschmidt, M. Nassiri, M. S. Stitt, K. Wasserloos, S. C. Watkins, B. R. Pitt, and N. Jahroudi Sequences in Intron 51 of the von Willebrand Factor Gene Target Promoter Activation to a Subset of Lung Endothelial Cells in Transgenic Mice J. Biol. Chem., February 1, 2008; 283(5): 2741 - 2750. [Abstract] [Full Text] [PDF] T. Ohno, Y. Onishi, and N. Ishida A novel E4BP4 element drives circadian expression of mPeriod2 Nucleic Acids Res., January 28, 2007; 35(2): 648 - 655. [Abstract] [Full Text] [PDF] K. Hagihara, T. Nishikawa, Y. Sugamata, J. Song, T. Isobe, T. Taga, and K. Yoshizaki Essential role of STAT3 in cytokine-driven NF-{kappa}B-mediated serum amyloid A gene expression Genes Cells, November 1, 2005; 10(11): 1051 - 1063. [Abstract] [Full Text] [PDF]

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