Genome-wide evaluation of altered chromatin looping in the post-stroke mouse cortex using Hi-C chromatin conformation capture
Recent advances in high-throughput transcriptomics have revealed extensive gene expression changes during cerebral ischemia. However, the changes in 3D chromatin architecture and long-range chromatin looping between genes and distal regulatory elements that drive these gene expression changes remain virtually unexplored. In this study, we mapped the landscape of altered 3D chromatin looping the in the ischemic cortex and evaluated its contributions to post-stroke transcriptional changes. We used genome-wide chromatin conformation capture (Hi-C) to profile changes in the 3D chromatin architecture in the cerebral cortex of adult mice following a 1 h middle cerebral artery occlusion and 6 h of reperfusion, or sham surgery. We identified a total of 15,592 loops in the stroke group with a mean enrichment core of 6.108, and these included 1973 promoter-promoter contacts, 7857 enhancer-enhancer contacts, and 5762 enhancer-promoter contacts. In the sham group, there were 14,779 chromatin loops with a mean enrichment score of 5.473, including 1714 promoter-promoter contacts, 8597  enhancer-enhancer contacts, and 4468 enhancer-promoter contacts. Together, our study represents the first genome-wide evaluation of 3D chromatin looping following stroke. Overall design: Genome-wide Hi-C was performed on ipsilateral cortices isolated from mice subjected to 1 h middle cerebral artery occlusion (MCAO) using the intraluminal filament model followed by 6 hours of reperfusion, as well as from sham animals that underwent the full surgical procedure except filament insertion.