Hierarchical Chromatin Rewiring Orchestrates Early Transcriptional Regulation in Mouse Cerebral Cortex Following Focal Ischemia

In this study, we profile genome-wide chromatin organization and transcriptional activity in the mouse cerebral cortex following transient middle cerebral artery occlusion (tMCAO). Using Hi-C alongside prior transcriptomic data and cis-regulatory annotations at early reperfusion time points, we show that ischemic injury triggers hierarchical reorganization of chromatin structure, including alterations in compartmentalization, topologically associating domains, and enhancer–promoter interactions.

These structural changes are temporally coordinated with early gene expression programs involved in inflammation, stress response, and neuronal remodeling. Our data reveal that transcriptional activation following ischemia is constrained and guided by multi-scale chromatin architecture, providing a systems-level framework for understanding genome regulation during acute brain injury.