Our paper on gene regulatory networks to understand disease mechanism of pulmonary arterial hypertension (PAH) is out!
This work results from a collaboration with 2 groups at Stanford. Check it out here: https://www.nature.com/articles/s41467-020-15463-x
Our main take-home messages from the study:
1) Chromatin is more sensitive than RNA to capture a cell’s regulatory state
2) Chromatin changes are best interpreted in the context of a gene regulatory network
3) The PAH phenotype in pulmonary arterial endothelial cells involves a complex network of different processes that are reflected in epigenetic marks
A striking part of this study was that we didn’t find any detectable difference in gene expression, yet huge changes in H3K27ac marks, which recapitulated differential activity in almost all known PAH TFs (using diffTF) and suggested a complete rewiring of the gene regulatory network. The changes in the regulatory network converge on endothelial to mesenchymal transition and response to signaling. And follow-up experiments confirmed that genes with differential H3K27ac in enhancers show a differential response to endogenous stimuli despite the no difference at baseline expression.