Epigenetics of Endothelial Dysfunction

epigenetics Endothelial Cell Polycomb

dr. G. Krenning
Dr. M.C. Harmsen
M. Maleszewska

Nature of the research:
This is a fundamental research project investigating the influence of Polycomb Repressive Comlex-2 (specifically methyltransferase Ezh2) on Endothelial Function.

Fields of study:
medical biology molecular biology vascular medicine

Background / introduction
Endothelial cells line the inside of all blood vessels. Endothelial cells have a number of specific cell functions, that are pivotal in maintaining homeostasis. These functions are, amongst others, maintenance of the blood vessel permeability, regulation of the vascular tone, inhibiting inflammation and the regulation of thrombogenicity. Disruption of endothelial cell functions, i.e. endothelial dysfunction, is observed in all chronic diseases and restoration of endothelial homeostasis is associated with disease alleviation.
The Polycomb methyltransferase Ezh2 is disregulated during endothelial dysfunction, resulting in reduced methylation of H3K27. This project aims to identify the genes that are silenced by Ezh2 during homeostasis and that are increased during endothelial dysfunction.
Research question / problem definition
This research project focusses on the following research questions:
1. Which genes in endothelial cells are under control of methyltransferase Ezh2?
2. What environmental factors influence the expression of Ezh2 and how do they influence endothelial dysfunction?
3. Can restoration of Ezh2 ameliorate endothelial dysfunction?
RNAi approaches will be used to reduce Ezh2 expression in Endothelial cells. Molecular biology techniques (i.e. qPCR, Western Blot) will be used to study downstream effects of Ezh2 loss-of-function. Chromatin immunoprecipitation (ChIP) of H3K28Me3 followed by promotor analysis will be used to determine gene targets of Ezh2.
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