DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

@article{Zhao2017DNAMD,
  title={DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons},
  author={Jian-Yuan Zhao and Lingli Liang and Xiyao Gu and Zhisong Li and Shaogen Wu and Linlin Sun and Fidelis E. Atianjoh and Jian Feng and Kai Mo and Shushan Jia and Brianna Marie Lutz and Alex Y. Bekker and Eric J. Nestler and Yuan-Xiang Tao},
  journal={Nature Communications},
  year={2017},
  volume={8}
}
Nerve injury induces changes in gene transcription in dorsal root ganglion (DRG) neurons, which may contribute to nerve injury-induced neuropathic pain. DNA methylation represses gene expression. Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor 1. Blocking this increase prevents nerve injury-induced methylation of the voltage-dependent… 

Contribution of DNMT1 to Neuropathic Pain Genesis Partially through Epigenetically Repressing Kcna2 in Primary Afferent Neurons

TLDR
It is shown that DNMT1, a canonical maintenance methyltransferase, acts as the de novo DNMT and is required for neuropathic pain genesis likely through repressing at least DRG Kcna2 gene expression in male mice.

Nerve injury–induced epigenetic silencing of opioid receptors controlled by DNMT3a in primary afferent neurons

TLDR
It is shown that blocking the nerve injury–induced increase in DRG DNMT3a (a de novo DNMT) rescued the expression of Oprm1 and Oprk1 mRNAs and their respective encoding mu-opioid receptor (MOR) and kappa-operative receptor (KOR) proteins in the injured DRG.

The transcription factor C/EBPβ in the dorsal root ganglion contributes to peripheral nerve trauma–induced nociceptive hypersensitivity

TLDR
It is reported that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG, which suggests that C/EPBβ is an endogenous initiator of neuropathic pain and could be a potential target for the prevention and treatment of this disorder.

N6‐Methyladenosine Demethylase FTO Contributes to Neuropathic Pain by Stabilizing G9a Expression in Primary Sensory Neurons

TLDR
It is reported that peripheral nerve injury increases the expression of the m6A demethylase fat‐mass and obesity‐associated proteins (FTO) in the injured DRG via the activation of Runx1, a transcription factor that binds to the Fto gene promoter.

MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons

TLDR
It is reported here thatMBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical, heat, cold, and capsaicin stimuli and the blunted nerve injury-induced pain hypersensitivities.

Contribution of dorsal root ganglion octamer transcription factor 1 to neuropathic pain after peripheral nerve injury

TLDR
Findings indicate that octamer transcription factor 1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG and may serve as a potential target for therapeutic treatments against neuropathicPain.

TET1 Overexpression Mitigates Neuropathic Pain Through Rescuing the Expression of μ-Opioid Receptor and Kv1.2 in the Primary Sensory Neurons

TLDR
Findings suggest that DRG TET1 overexpression mitigated neuropathic pain likely through rescue of MOR and Kv1.2 expression in the ipsilateral DRG.

A nerve injury–specific long noncoding RNA promotes neuropathic pain by increasing Ccl2 expression

TLDR
NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathy pain management.

MMP24 Contributes to Neuropathic Pain in an FTO-Dependent Manner in the Spinal Cord Neurons

TLDR
SNL promoted the m6A eraser FTO binding to the Mmp24 mRNA, which subsequently facilitated the translation of MMP24 in the spinal cord, and ultimately contributed to neuropathic pain genesis.
...

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