Signatures of altered DNA methylation gene expression after central and peripheral nerve injury

Abstract

Nerve damage can lead to movement and sensory dysfunction, with high morbidity and disability rates causing severe burdens on patients, families, and society. DNA methylation is a kind of epigenetics, and a great number of previous studies have demonstrated that DNA methylation plays an important role in the process of nerve regeneration and remodeling. However, compared with the central nervous system, the peripheral nervous system shows stronger recovery after injury, which is related to the complex microenvironment and epigenetic changes occurring at the site of injury. Therefore, what common epigenetic changes between the central and peripheral nervous systems remain to be elucidated. We first screened differential methylation genes after spinal cord injury and sciatic nerve injury using whole‐genome bisulfite sequencing and methylated DNA immunoprecipitation sequencing, respectively. Subsequently, a total of 16 genes had the same epigenetic changes after spinal cord injury and sciatic nerve injury. The Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. Furthermore, a protein−protein interaction network analysis indicated that Dnm3, Ntrk3, Smurf1, Dpysl2, Kalrn, Shank1, Dlg2, Arsb, Reln, Bmp5, Numbl, Prickle2, Map6, and Htr7 were the core genes. These outcomes may provide novel insights into the molecular mechanism of the subacute phase of nerve injury. These verified genes can offer potential diagnostic and therapeutic targets for nerve injury.

Identification of adhesion‑associated DNA methylation patterns in the peripheral nervous system

“…DNA methylation, histone modification and non-coding RNA regulation have been studied in previous epigenetic research (31,(52)(53)(54). In our previous studies, genome-wide methylation analyses and iTRAQ-based proteomics profiling of Schwann cells after PNI were performed (23,35).…”

“…DNA methylation, which directs transcriptional silencing via heterochromatin formation, is a genetic marker for the growth and development of a number of eukaryotes (27)(28)(29). As one of the earliest epigenetic modifications to be recognized, DNA methylation has been observed in numerous organisms (30,31). Methylation of eukaryotic DNA typically occurs at position 5 of cytosine to produce 5-methylcytosine (32).…”

Combination of single-cell and bulk RNA seq reveals the immune infiltration landscape and targeted therapeutic drugs in spinal cord injury

“…Whether neurons and axons can regenerate after SCI depend not only on their original growth ability, but also on the neurovascular microenvironment and epigenetic changes, which is mainly embodied in DNA methylation and histone acetylation ( 27 ). Among these, DNA methylation affects many aspects of neural stem cell maintenance and proliferation, neuronal differentiation and maturation, and synaptogenesis ( 28 ). Decitabine is a demethylating drug that can inhibit DNA methyltransferase, reduce DNA methylation, and inhibit tumor cell proliferation, and it has been the primary drug for elderly AML patients ( 29 ).…”

Epigenome-Wide Association Study Reveals Differential Methylation Sites and Association of Gene Expression Regulation with Ischemic Moyamoya Disease in Adults

“…( 8 ). Some studies have indicated the importance of investigating the effect of pathways of interest on the occurrence and development of MMD ( 14 – 16 ). However, information regarding the significantly different methylation sites in adult ischemic MMD remains scarce.…”