title: G9a participates in nerve injury-induced Kcna2 downregulation in primary sensory neurons.
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.
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Lingli
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Xiyao
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jian-Yuan
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Shaogen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Xuerong
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Jifang
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Mo
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Brianna Marie
authors.initials: BM
authors.lastname: Lutz
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Bekker
authors.affiliation: Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.|Departments of Cell Biology &Molecular Medicine and Physiology, Pharmacology &Neuroscience, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA.
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
mesh_terms: D000200:Action Potentials; D000818:Animals; D019771:Axotomy; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006967:Hypersensitivity / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating; D051663:Kv1.2 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008026:Ligation; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000473:pathology*; D013127:Spinal Nerves / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology
chemical_list: D006657:Histones; C496970:Kcna2 protein, mouse; D051663:Kv1.2 Potassium Channel; D012333:RNA, Messenger; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine