Identification of Regulatory Elements in Primary Sensory Neurons Involved in Trauma-Induced Neuropathic Pain

Kimberly E Stephens; Cedric Moore; David A Vinson; Bryan E White; Zachary Renfro; Weiqiang Zhou; Zhicheng Ji; Hongkai Ji; Heng Zhu; Yun Guan; Sean D Taverna

doi:10.1007/s12035-023-03673-5

Identification of Regulatory Elements in Primary Sensory Neurons Involved in Trauma-Induced Neuropathic Pain

Mol Neurobiol. 2024 Mar;61(3):1845-1859. doi: 10.1007/s12035-023-03673-5. Epub 2023 Oct 4.

Authors

Kimberly E Stephens^#^{1

2

3

4}, Cedric Moore^{5

6}, David A Vinson^{5

7}, Bryan E White^{8

9}, Zachary Renfro^{8

9

10}, Weiqiang Zhou¹¹, Zhicheng Ji^{11

12}, Hongkai Ji¹¹, Heng Zhu⁵, Yun Guan^{13

14}, Sean D Taverna^{15

16}

Affiliations

¹ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. kestephens@uams.edu.
² Arkansas Children's Research Institute, 13 Children's Way, Slot 512-47, Little Rock, AR, 72202, USA. kestephens@uams.edu.
³ Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. kestephens@uams.edu.
⁴ Center for Epigenetics, Johns Hopkins University, Baltimore, MD, USA. kestephens@uams.edu.
⁵ Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA.
⁶ , Present address: 20400 Century Blvd, Suite 120, Germantown, MD, USA.
⁷ Center for Epigenetics, Johns Hopkins University, Baltimore, MD, USA.
⁸ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁹ Arkansas Children's Research Institute, 13 Children's Way, Slot 512-47, Little Rock, AR, 72202, USA.
¹⁰ Present address: School of Medicine, Stanford University, Palo Alto, CA, USA.
¹¹ Department of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
¹² Present address: Department of Biostatistics and Bioinformatics, School of Medicine, Duke University, Durham, NC, USA.
¹³ Department of Anesthesiology and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. yguan1@jhmi.edu.
¹⁴ Department of Neurological Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. yguan1@jhmi.edu.
¹⁵ Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD, 21205, USA. staverna@jhmi.edu.
¹⁶ Center for Epigenetics, Johns Hopkins University, Baltimore, MD, USA. staverna@jhmi.edu.

^# Contributed equally.

Abstract

Chronic pain is a significant public health issue that is often refractory to existing therapies. Here we use a multiomic approach to identify cis-regulatory elements that show differential chromatin accessibility and reveal transcription factor (TF) binding motifs with functional regulation in the rat dorsal root ganglion (DRG), which contain cell bodies of primary sensory neurons, after nerve injury. We integrated RNA-seq to understand how differential chromatin accessibility after nerve injury may influence gene expression. Using TF protein arrays and chromatin immunoprecipitation-qPCR, we confirmed C/EBPγ binding to a differentially accessible sequence and used RNA-seq to identify processes in which C/EBPγ plays an important role. Our findings offer insights into TF motifs that are associated with chronic pain. These data show how interactions between chromatin landscapes and TF expression patterns may work together to determine gene expression programs in rat DRG neurons after nerve injury.

Keywords: CEBPG; Chromatin accessibility; Chronic constriction injury; Dorsal root ganglion; Epigenetics; Neuropathic pain.

MeSH terms

Animals
Chromatin / metabolism
Chronic Pain* / metabolism
Ganglia, Spinal / metabolism
Neuralgia* / metabolism
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells / metabolism

Substances

Chromatin