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Research Articles, Development/Plasticity/Repair

Role of Myc Proto-Oncogene as a Transcriptional Hub to Regulate the Expression of Regeneration-Associated Genes following Preconditioning Peripheral Nerve Injury

Hae Young Shin, Min Jung Kwon, Eun Mi Lee, Kyung Kim, Young Joo Oh, Hyung Soon Kim, Dong Hoon Hwang and Byung Gon Kim
Journal of Neuroscience 20 January 2021, 41 (3) 446-460; DOI: https://doi.org/10.1523/JNEUROSCI.1745-20.2020
Hae Young Shin
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Min Jung Kwon
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Eun Mi Lee
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Kyung Kim
3Department of Biomedical Informatics, Ajou University school of Medicine, Suwon, 16499, Republic of Korea
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Young Joo Oh
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Hyung Soon Kim
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Dong Hoon Hwang
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
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Byung Gon Kim
1Department of Brain Science, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
2Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea
4Department of Neurology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea
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Abstract

Preconditioning peripheral nerve injury enhances the intrinsic growth capacity of DRGs sensory axons by inducing transcriptional upregulation of the regeneration-associated genes (RAGs). However, it is still unclear how preconditioning injury leads to the orchestrated induction of many RAGs. The present study identified Myc proto-oncogene as a transcriptional hub gene to regulate the expression of a distinct subset of RAGs in DRGs following the preconditioning injury. We demonstrated that c-MYC bound to the promoters of certain RAGs, such as Jun, Atf3, and Sprr1a, and that Myc upregulation following SNI preceded that of the RAGs bound by c-MYC. Marked DNA methylation of the Myc exon 3 sequences was implicated in the early transcriptional activation and accompanied by open histone marks. Myc deletion led to a decrease in the injury-induced expression of a distinct subset of RAGs, which were highly overlapped with the list of RAGs that were upregulated by Myc overexpression. Following dorsal hemisection spinal cord injury in female rats, Myc overexpression in DRGs significantly prevented the retraction of the sensory axons in a manner dependent on its downstream RAG, June. Our results suggest that Myc plays a critical role in axon regeneration via its transcriptional activity to regulate the expression of a spectrum of downstream RAGs and subsequent effector molecules. Identification of more upstream hub transcription factors and the epigenetic mechanisms specific for individual hub transcription factors would advance our understanding of how the preconditioning injury induces orchestrated upregulation of RAGs.

  • axon regeneration
  • axon retraction
  • hub transcription factor
  • Myc
  • preconditioning injury
  • regeneration-associated genes

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The Journal of Neuroscience: 41 (3)
Journal of Neuroscience
Vol. 41, Issue 3
20 Jan 2021
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Role of Myc Proto-Oncogene as a Transcriptional Hub to Regulate the Expression of Regeneration-Associated Genes following Preconditioning Peripheral Nerve Injury
Hae Young Shin, Min Jung Kwon, Eun Mi Lee, Kyung Kim, Young Joo Oh, Hyung Soon Kim, Dong Hoon Hwang, Byung Gon Kim
Journal of Neuroscience 20 January 2021, 41 (3) 446-460; DOI: 10.1523/JNEUROSCI.1745-20.2020

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Role of Myc Proto-Oncogene as a Transcriptional Hub to Regulate the Expression of Regeneration-Associated Genes following Preconditioning Peripheral Nerve Injury
Hae Young Shin, Min Jung Kwon, Eun Mi Lee, Kyung Kim, Young Joo Oh, Hyung Soon Kim, Dong Hoon Hwang, Byung Gon Kim
Journal of Neuroscience 20 January 2021, 41 (3) 446-460; DOI: 10.1523/JNEUROSCI.1745-20.2020
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Keywords

  • axon regeneration
  • axon retraction
  • hub transcription factor
  • Myc
  • preconditioning injury
  • regeneration-associated genes

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