Global analysis of shear stress regulated enhancer elements in endothelial cells

Endothelial phenotypes under static conditions (left) and after shear stress exposure for 24 hours (right).
© Hans-Joachim Schnittler, Arndt Siekmann

Principal investigators: Hans-Joachim Schnittler, Arndt Siekmann
Project time: 07/2014 - 06/2017
Project code: FF-2014-15

Several key processes during vascular development and homeostasis are controlled by endothelial cell responses to shear stress. Despite this fundamental influence of biomechanical cues on endothelial biology, we still lack an understanding of how endothelial cells respond to changes in hemodynamics and how these changes ultimately lead to changes in the cell's transcriptional program. In this proposal, we aim at understanding the positive and negative regulation of gene transcription in endothelial cells by changes in hemodynamics. In order to do so, we will perform genome wide mapping of shear stress induced changes in active cis regulatory elements in endothelial cells using Chromatin immunoprecipitation followed by sequencing (ChIP-Seq). Subsequently we compare our dataset with available gene expression data of flow-induced genes and validate identified cis-regulatory elements using both cultured human endothelium and endothelium from zebrafish embryos. Ultimately, we aim at determining the transcriptional logic underlying shear stress induced gene expression by identifying the transcription factors mediating this response.