Figure 10.

Schematic shows the proposed mechanism by which ZNF382 participates in neuropathic pain. ZNF382 is down-regulated in injured DRG neurons after peripheral nerve injury. ZNF382 down-regulation reduces the ZNF382/HDAC1/SETDB1 complex formation and diminishes the corepressors occupancy in Cxcl13 gene promoter and 5′-UTR at the structural basis of the silencer–promoter loop. The latter increases the ac-H3 enrichment on F11 and decreases the H3K9me3 enrichment on F10 in Cxcl13 gene promoter and 5′-UTR, resulting in the transcriptional activation of Cxcl13 in injured DRG neurons. ZNF382-mediated increased CXCL13 acts on the neuron-expressed receptor CXCR5 to promote DRG neuronal hyperactivation, which eventually contributes to central hyperactivation and pain hypersensitivity. Gray color pattern: potential unknown components.