In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-06-06)
Kurzfassung:
Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities and functional states remain poorly understood. Here, we report a genome-wide assessment of regulatory landscapes of primary human aortic endothelial cells (HAECs) under basal and activated conditions, enabling inference of transcription factor networks that direct homeostatic and pro-inflammatory programs. We demonstrate that 43% of detected enhancers are EC-specific and contain SNPs associated to cardiovascular disease and hypertension. We provide evidence that AP1, ETS, and GATA transcription factors play key roles in HAEC transcription by co-binding enhancers associated with EC-specific genes. We further demonstrate that exposure of HAECs to oxidized phospholipids or pro-inflammatory cytokines results in signal-specific alterations in enhancer landscapes and associate with coordinated binding of CEBPD, IRF1, and NFκB. Collectively, these findings identify cis-regulatory elements and corresponding trans-acting factors that contribute to EC identity and their specific responses to pro-inflammatory stimuli.
Materialart:
Online-Ressource
ISSN:
2050-084X
DOI:
10.7554/eLife.22536.001
DOI:
10.7554/eLife.22536.002
DOI:
10.7554/eLife.22536.003
DOI:
10.7554/eLife.22536.004
DOI:
10.7554/eLife.22536.005
DOI:
10.7554/eLife.22536.006
DOI:
10.7554/eLife.22536.007
DOI:
10.7554/eLife.22536.008
DOI:
10.7554/eLife.22536.009
DOI:
10.7554/eLife.22536.010
DOI:
10.7554/eLife.22536.011
DOI:
10.7554/eLife.22536.012
DOI:
10.7554/eLife.22536.013
DOI:
10.7554/eLife.22536.014
DOI:
10.7554/eLife.22536.015
DOI:
10.7554/eLife.22536.016
DOI:
10.7554/eLife.22536.017
DOI:
10.7554/eLife.22536.018
DOI:
10.7554/eLife.22536.019
DOI:
10.7554/eLife.22536.020
DOI:
10.7554/eLife.22536.021
DOI:
10.7554/eLife.22536.022
DOI:
10.7554/eLife.22536.023
DOI:
10.7554/eLife.22536.024
DOI:
10.7554/eLife.22536.025
DOI:
10.7554/eLife.22536.026
DOI:
10.7554/eLife.22536.027
DOI:
10.7554/eLife.22536.028
Sprache:
Englisch
Verlag:
eLife Sciences Publications, Ltd
Publikationsdatum:
2017
ZDB Id:
2687154-3