Chromatin interaction landscape of epimorphic regeneration in teleost fish

Reorganization of chromatin architecture—including chromatin loops, topologically associating domains (TADs), and A/B compartments—has been increasingly linked to development and cell differentiation. However, how chromatin architecture reorganizes during the shift from homeostasis to regeneration remains poorly characterized. Here, we used zebrafish fin regeneration as a model to systematically investigate, via micro-C, the chromatin architecture associated with blastema formation. Our analyses unveiled that the alteration of chromatin looping upon amputation was dominant compared with that of TADs and compartments. Genes directly linked to injury-altered loop interactions, including essential regeneration regulators, were mainly related to morphogenesis and cell division. A side-by-side comparison between zebrafish and African killifish uncovered conserved and species-specific chromatin reorganization following injury. Notably, perturbing injury-altered loop interactions at the il11a locus suppressed its expression and impaired fin regeneration efficiency. Further, CTCF/CTCFL and Atf7 binding motifs were the top shared motifs enriched in regeneration-altered loop anchors. Our study uncovers the landscape of chromatin interactions during fin regeneration.