Cargando…
Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain
BACKGROUND: Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. METHODS: To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system,...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390277/ https://www.ncbi.nlm.nih.gov/pubmed/34446036 http://dx.doi.org/10.1186/s12974-021-02228-6 |
_version_ | 1783743056753721344 |
---|---|
author | Stephens, Kimberly E. Zhou, Weiqiang Renfro, Zachary Ji, Zhicheng Ji, Hongkai Guan, Yun Taverna, Sean D. |
author_facet | Stephens, Kimberly E. Zhou, Weiqiang Renfro, Zachary Ji, Zhicheng Ji, Hongkai Guan, Yun Taverna, Sean D. |
author_sort | Stephens, Kimberly E. |
collection | PubMed |
description | BACKGROUND: Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. METHODS: To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund’s adjuvant (CFA) in rats. RESULTS: Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. CONCLUSIONS: Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02228-6. |
format | Online Article Text |
id | pubmed-8390277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-83902772021-08-27 Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain Stephens, Kimberly E. Zhou, Weiqiang Renfro, Zachary Ji, Zhicheng Ji, Hongkai Guan, Yun Taverna, Sean D. J Neuroinflammation Research BACKGROUND: Efforts to understand genetic variability involved in an individual’s susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. METHODS: To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund’s adjuvant (CFA) in rats. RESULTS: Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. CONCLUSIONS: Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02228-6. BioMed Central 2021-08-26 /pmc/articles/PMC8390277/ /pubmed/34446036 http://dx.doi.org/10.1186/s12974-021-02228-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Stephens, Kimberly E. Zhou, Weiqiang Renfro, Zachary Ji, Zhicheng Ji, Hongkai Guan, Yun Taverna, Sean D. Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title | Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title_full | Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title_fullStr | Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title_full_unstemmed | Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title_short | Global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
title_sort | global gene expression and chromatin accessibility of the peripheral nervous system in animal models of persistent pain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390277/ https://www.ncbi.nlm.nih.gov/pubmed/34446036 http://dx.doi.org/10.1186/s12974-021-02228-6 |
work_keys_str_mv | AT stephenskimberlye globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT zhouweiqiang globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT renfrozachary globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT jizhicheng globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT jihongkai globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT guanyun globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain AT tavernaseand globalgeneexpressionandchromatinaccessibilityoftheperipheralnervoussysteminanimalmodelsofpersistentpain |