Myelination of the peripheral nervous system is required for axonal function and 
long term stability. After peripheral nerve injury, Schwann cells transition 
from axon myelination to a demyelinated state that supports neuronal survival 
and ultimately remyelination of axons. Reprogramming of gene expression patterns 
during development and injury responses is shaped by the actions of distal 
regulatory elements that integrate the actions of multiple transcription 
factors. We used ChIP-seq to measure changes in histone H3K27 acetylation, a 
mark of active enhancers, to identify enhancers in myelinating rat peripheral 
nerve and their dynamics after demyelinating nerve injury. Analysis of 
injury-induced enhancers identified enriched motifs for c-Jun, a transcription 
factor required for Schwann cells to support nerve regeneration. We identify a 
c-Jun-bound enhancer in the gene for Runx2, a transcription factor induced after 
nerve injury, and we show that Runx2 is required for activation of other induced 
genes. In contrast, enhancers that lose H3K27ac after nerve injury are enriched 
for binding sites of the Sox10 and early growth response 2 (Egr2/Krox20) 
transcription factors, which are critical determinants of Schwann cell 
differentiation. Egr2 expression is lost after nerve injury, and many 
Egr2-binding sites lose H3K27ac after nerve injury. However, the majority of 
Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors 
maintain active enhancer status after nerve injury. The global epigenomic 
changes in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate 
the effects of transcription factors that control Schwann cell myelination and 
peripheral nervous system responses to nerve injury.