Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium |
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Authors: | J E Fish P A Marsden |
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Institution: | (1) Department of Medical Biophysics, St. Michael’s Hospital and University of Toronto, Toronto, Canada;(2) Renal Division and Department of Medicine, Rm 7358, Medical Sciences Building, 1 King’s College Circle, Toronto, Ontario, M5S 1A8, Canada |
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Abstract: | The vascular endothelium plays a crucial role in regulating normal blood vessel physiology. The gene products responsible
are commonly expressed exclusively, or preferentially, in this cell type. However, despite the importance of regulated gene
expression in the vascular endothelium, relatively little is known about the mechanisms that restrict endothelial-specific
gene expression to this cell type. While significant progress has been made towards understanding the regulation of endothelial
genes through cis/trans paradigms, it has become apparent that additional mechanisms must also be operative. For example,
chromatin-based mechanisms, including cell-specific DNA methylation patterns and post-translational histone modifications,
have recently been demonstrated to play important roles in the cell-specific expression of endothelial nitric oxide synthase
(eNOS). This review investigates the involvement of epigenetic regulatory mechanisms in vascular endothelial cell-specific
gene expression using eNOS as a prototypical model, and will address the possible contributions of these pathways to diseases
of the vasculature.
Received 13 September 2005; received after revision 13 October 2005; accepted 19 October 2005 |
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Keywords: | Chromatin epigenetics endothelium gene regulation histone code endothelial nitric oxide synthase sONE cell-specific |
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