PMID- 32974606
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2516-8657 (Electronic)
IS  - 2516-8657 (Linking)
VI  - 13
DP  - 2020
TI  - The Role of DNA Methylation in Transcriptional Regulation of Pro-Nociceptive 
      Genes in Rat Trigeminal Ganglia.
PG  - 2516865720938677
LID - 10.1177/2516865720938677 [doi]
LID - 2516865720938677
AB  - Epigenetic modulation by DNA methylation is associated with aberrant gene 
      expression in sensory neurons, which consequently leads to pathological pain 
      responses. In this study, we sought to investigate whether peripheral 
      inflammation alters global DNA methylation in trigeminal ganglia (TG) and results 
      in abnormal expression of pro-nociceptive genes. Our results show that peripheral 
      inflammation remotely reduced the level of global DNA methylation in rat TG with 
      a concurrent reduction in DNMT1 and DNMT3a expression. Using unbiased steps, we 
      selected the following pro-nociceptive candidate genes that are potentially 
      regulated by DNA methylation: TRPV1, TRPA1, P2X3, and PIEZO2. Inhibition of DNMT 
      with 5-Aza-dC in dissociated TG cells produced dose-dependent upregulation of 
      TRPV1, TRPA1, and P2X3. Systemic treatment of animals with 5-Aza-dC significantly 
      increased the expression of TRPV1, TRPA1, and PIEZO2 in TG. Furthermore, the 
      overexpression of DNMT3a, as delivered by a lentiviral vector, significantly 
      downregulated TRPV1 and PIEZO2 expression and also reliably decreased TRPA1 and 
      P2X3 transcripts. MeDIP revealed that this overexpression also significantly 
      enhanced methylation of CGIs associated with TRPV1 and TRPA1. In addition, 
      bisulfite sequencing data indicated that the CGI associated with TRPA1 was 
      methylated in a pattern catalyzed by DNMT3a. Taken together, our results show 
      that all 4 pro-nociceptive genes are subject to epigenetic modulation via DNA 
      methylation, likely via DNMT3a under inflammatory conditions. These findings 
      provide the first evidence for the functional importance of DNA methylation as an 
      epigenetic factor in the transcription of pro-nociceptive genes in TG that are 
      implicated in pathological orofacial pain responses.
CI  - (c) The Author(s) 2020.
FAU - Bai, Guang
AU  - Bai G
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
FAU - Ross, Holly
AU  - Ross H
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
FAU - Zhang, Youping
AU  - Zhang Y
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
FAU - Lee, KiSeok
AU  - Lee K
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
FAU - Ro, Jin Y
AU  - Ro JY
AD  - Department of Neural and Pain Sciences, University of Maryland Dental School, 
      Baltimore, MD, USA.
LA  - eng
PT  - Journal Article
DEP - 20200910
PL  - United States
TA  - Epigenet Insights
JT  - Epigenetics insights
JID - 101735398
PMC - PMC7495519
OTO - NOTNLM
OT  - DNA methylation
OT  - inflammation
OT  - pain
OT  - sensory ganglia
COIS- Declaration of Conflicting Interests:The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2020/09/26 06:00
MHDA- 2020/09/26 06:01
PMCR- 2020/09/10
CRDT- 2020/09/25 06:05
PHST- 2020/04/18 00:00 [received]
PHST- 2020/06/04 00:00 [accepted]
PHST- 2020/09/25 06:05 [entrez]
PHST- 2020/09/26 06:00 [pubmed]
PHST- 2020/09/26 06:01 [medline]
PHST- 2020/09/10 00:00 [pmc-release]
AID - 10.1177_2516865720938677 [pii]
AID - 10.1177/2516865720938677 [doi]
PST - epublish
SO  - Epigenet Insights. 2020 Sep 10;13:2516865720938677. doi: 
      10.1177/2516865720938677. eCollection 2020.