Axon regeneration is a necessary step toward functional recovery after spinal cord injury. The AP-1 transcription factor c-Jun has long been known to play an important role in directing the transcriptional response of Dorsal Root Ganglion (DRG) neurons to peripheral axotomy that results in successful axon regeneration. Here we performed ChIPseq for Jun in mouse DRG neurons after a sciatic nerve crush or sham surgery in order to measure the changes in Jun's DNA binding in response to peripheral axotomy. We found that the majority of Jun's injury-responsive changes in DNA binding occur at putative enhancer elements, rather than proximal to transcription start sites. We also used a series of single polypeptide chain tandem transcription factors to test the effects of different Jun-containing dimers on neurite outgrowth in DRG, cortical and hippocampal neurons. These experiments demonstrated that dimers composed of Jun and Atf3 promoted neurite outgrowth in rat CNS neurons as well as mouse DRG neurons. Our work provides new insight into the mechanisms underlying Jun's role in axon regeneration.

轴突再生是脊髓损伤后恢复功能的必要步骤。众所周知，AP-1转录因子c-Jun在引导背根神经节（DRG）神经元对周围轴突的转录反应中起重要作用，从而导致轴突再生成功。在这里，我们在坐骨神经挤压或假手术后在小鼠DRG神经元中对Jun进行了ChIPseq，以测量响应外周轴切术的Jun DNA结合的变化。我们发现，DNA结合中Jun的大多数损伤反应性变化发生在推定的增强子元件上，而不是在转录起始位点附近。我们还使用了一系列单多肽串联串联转录因子来测试不同的含Jun的二聚体对DRG中神经突生长的影响，皮质和海马神经元。这些实验证明，由Jun和Atf3组成的二聚体促进了大鼠CNS神经元和小鼠DRG神经元的神经突生长。我们的工作为Jun在轴突再生中的作用机理提供了新的见解。