Role of a 5'-enhancer in the transcriptional regulation of the human endothelial cell protein C receptor gene

Blood
Luigina R MollicaDavid A Lane

Abstract

The endothelial cell protein C receptor (EPCR) is expressed by endothelial cells of large blood vessels and by hematopoietic stem cells. DNaseI hypersensitive (DH) site mapping across 38 kb of the human EPCR gene (hEPCR) locus identified 3 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 endothelial cells (ECs) and immature hematopoietic cell lines. Transgenes expressing LacZ under the control of -5.5HS coupled to either PP or the SV40 promoter were able to direct beta-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...Continue Reading

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Citations

Jun 17, 2009·Journal de la Société de biologie·Alexandra Le Bras, Fabrice Soncin
Nov 1, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Maryam DendanaTouhami Mahjoub
Aug 29, 2007·Journal of Thrombosis and Haemostasis : JTH·J T B Crawley
Mar 28, 2008·Journal of Thrombosis and Haemostasis : JTH·J T B Crawley, M Efthymiou
May 30, 2015·Cellular and Molecular Life Sciences : CMLS·Joseph M Miano, Xiaochun Long
Feb 17, 2009·Developmental Cell·Sarah De Val, Brian L Black
Feb 3, 2007·Circulation Research·Meenakshisundaram ThiyagarajanBerislav V Zlokovic
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Jan 24, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jérémy LagrangeVéronique Regnault
Nov 18, 2006·Blood·Laurent O MosnierJohn H Griffin

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