PATZ1 Reinstates a Growth-Permissive Chromatin Landscape in Adult Corticospinal Neurons After Injury

As CNS neurons mature, chromatin at growth-related genes becomes increasingly inaccessible—but when this shift happens, what drives it, and whether it’s reversible in adults has been unclear. We profiled chromatin accessibility in corticospinal neurons across development and found two distinct waves of restriction: a partial closure between P0–P4 and a stronger, widespread restriction from P7 into adulthood. We next asked if injury proximity influences chromatin remodeling. Distal (thoracic) injuries caused minimal changes, but proximal (intracortical) injuries triggered broad accessibility shifts, suggesting that injury site matters for epigenetic responsiveness. Finally, we tested whether the mature chromatin landscape could be reopened using PATZ1, a developmental transcription factor. Delivering PATZ1 post-injury led to marked chromatin remodeling—an 11.6-fold increase in H3K27ac at growth genes and targeted reorganisation of 3D genome architecture, including compartment switching and altered TADs. These changes were accompanied by transcriptional reactivation of growth programs. Together, our findings pinpoint when and how growth gene chromatin becomes restricted and show that it can be reactivated in adults using targeted interventions like PATZ1.