G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons

Lingli Liang, Xiyao Gu, Jian Yuan Zhao, Shaogen Wu, Xuerong Miao, Jifang Xiao, Kai Mo, Jun Zhang, Brianna Marie Lutz, Alex Bekker, Yuan Xiang Tao

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression. We showed here that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve injury-induced pain hypersensitivity. Mimicking this increase decreased Kcna2 mRNA and protein expression, reduced Kv current, and increased excitability in the DRG neurons and led to spinal cord central sensitization and neuropathic pain-like symptoms. G9a mRNA is co-localized with Kcna2 mRNA in the DRG neurons. These findings indicate that G9a contributes to neuropathic pain development through epigenetic silencing of Kcna2 in the axotomized DRG.

Original languageEnglish (US)
Article number37704
JournalScientific reports
Volume6
DOIs
StatePublished - Nov 22 2016

All Science Journal Classification (ASJC) codes

  • General

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