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

Axon regeneration fails in the adult central nervous system in part because chromatin at growth-associated loci becomes progressively inaccessible during maturation. Using bulk and single-nucleus ATAC-seq across developmental timepoints, we identified two postnatal waves of chromatin closure at growth-gene promoters and enhancers, coinciding with withdrawal of GC-stripe transcription factors. Comparing intracortical and thoracic spinal cord injuries, we found that lesion proximity to the soma determines the extent of chromatin reopening, with proximal injury reactivating an order of magnitude more regulatory elements. The stripe factor PATZ1 emerged as a molecular correlate of this distance effect. AAV-mediated PATZ1 delivery after distal injury reopened thousands of growth enhancers, deposited H3K27ac marks, and reorganised three-dimensional genome architecture, as revealed by CUT&RUN and Hi-C. Integrated single-nucleus RNA-seq showed that chromatin opening alone produces modest transcriptional changes, indicating that additional pro-growth factors are required. These findings establish epigenetic priming as a targetable prerequisite for CNS repair.