RT Journal Article
T1 Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension
A1 Reyes-Palomares, Armando
A1 Gu, Mingxia
A1 Grubert, Fabian
A1 Berest, Ivan
A1 Sa, Silin
A1 Kasowski, Maya
A1 Arnold, Christian
A1 Shuai, Mao
A1 Srivas, Rohith
A1 Miao, Simon
A1 Li, Dan
A1 Snyder, Michael P.
A1 Rabinovitch, Marlene
A1 Zaugg, Judith B.
K1 Sistema cardiovascular - Enfermedades
K1 Epigenética
AB Environmental and epigenetic factors often play an important role in polygenic disorders. However, how such factors affect disease-specific tissues at the molecular level remains to be understood. Here, we address this in pulmonary arterial hypertension (PAH). We obtain pulmonary arterial endothelial cells (PAECs) from lungs of patients and controls (n = 19), and perform chromatin, transcriptomic and interaction profiling. Overall, we observe extensive remodeling at active enhancers in PAH PAECs and identify hundreds of differentially active TFs, yet find very little transcriptomic changes in steady-state. We devise a disease-specific enhancer-gene regulatory network and predict that primed enhancers in PAH PAECs are activated by the differentially active TFs, resulting in an aberrant response to endothelial signals, which could lead to disturbed angiogenesis and endothelial-to-mesenchymal-transition. We validate these predictions for a selection of target genes in PAECs stimulated with TGF-β, VEGF or serotonin. Our study highlights the role of chromatin state and enhancers in disease-relevant cell types of PAH.
PB Nature Publishing Gro
YR 2020
FD 2020-04
LK https://hdl.handle.net/10630/41480
UL https://hdl.handle.net/10630/41480
LA eng
NO Reyes-Palomares, A., Gu, M., Grubert, F. et al. Remodeling of active endothelial enhancers is associated with aberrant gene-regulatory networks in pulmonary arterial hypertension. Nat Commun 11, 1673 (2020). https://doi.org/10.1038/s41467-020-15463-x
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026