|
|
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.
 Previous Article | Next Article 
Submitted October 15, 2002
Accepted October 18, 2004
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*
Department of Pathology and Molecular Medicine, Richardson Laboratories, Queen's University, Kingston, Ontario, Canada
* Corresponding author; email: lillicrap{at}cliff.path.queensu.ca.
Mechanisms of tissue-restricted patterns of 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 non-producing cells and promoter activity was highest in endothelial cells followed by megakaryocytes. Only basal VWF promoter activity was seen in non-endothelial cells. Here we identify a negative response element located at nts +96/+105 and demonstrate, using 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 which 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 co-ordinated 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:
|
|
|
|
 
F. Silvestris, P. Cafforio, M. De Matteo, N. Calvani, M. A. Frassanito, and F. Dammacco
Negative Regulation of the Osteoblast Function in Multiple Myeloma through the Repressor Gene E4BP4 Activated by Malignant Plasma Cells
Clin. Cancer Res.,
October 1, 2008;
14(19):
6081 - 6091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
