Hyperosmotic stress induces a large-scale rewiring of 3D chromatin interactions [Cut & Tag]

Cells rapidly adapt to hyperosmotic stress through coordinated molecular responses. To determine how three-dimensional (3D) chromatin structure contributes to this process, we profiled chromatin interactions, architectural protein occupancy, and transcriptional dynamics in human cells exposed to sorbitol-induced hyperosmotic stress. We performed time-resolved Hi-C to measure stress-induced remodeling of chromatin loops and domains, CUT&Tag to quantify CTCF, RAD21, YAP1, and H3K27ac occupancy at loop anchors, and RNA-seq to capture stress-responsive transcriptional programs. These data reveal global loss of pre-existing chromatin contacts and concurrent formation of de novo, transient loops enriched for retained CTCF and cohesin, as well as transcriptional responses that are temporally layered and largely decoupled from loop remodeling. This dataset provides a resource for investigating how nuclear architecture and transcriptional regulation respond to hyperosmotic stress.