Enhancer profiling uncovers JMJD1C as essential suppressor in neuropathic pain by targeting SOCS
Neuropathic pain (NP) is induced by injury or diseases of the somatosensory nervous system, which markedly impairs patients' quality of life.  Super-enhancers (SEs) are important cis-regulatory elements, but how they affect NP remains elusive.  Therefore, we aim to explore the molecular mechanism by which SEs are involved in NP progression and identify potential drug candidate targets.  We first established a rat model characterized with typical NP, and subsequently performed RNA-Seq and H3K27ac ChIP-Seq on spinal cord tissues of NP rats to analyze the active enhancers at the genome-wide level.  By analyzing the SE-associated genes involved in NP, combined with qPCR and double immunofluorescence staining results, we found that Jmjd1c is a core SE-associated regulator in NP progression, and Sox6 could activate Jmjd1c transcription by binding to its SE. Overall design: First of all, Spared nerve injury (SNI) induced NP rats and sham rats were established. Then, rats were deeply anesthetized with chloral hydrate, spinal cord tissue was obtained and fixed with 1% formaldehyde.  Nuclear chromatin was extracted and segmented to 100-400bp fragments by ultrasound, 5% was taken as input, and the remaining chromatin incubated together with the ChIP grade antibody: anti- H3K27ac.