ZBTB18 dysfunction promotes neuropathic pain via CHD4-based epigenetic disinhibition of CLIC1 channels in sensory neurons (ChIP-seq)

This study identifies a significant downregulation of ZBTB18 (zinc finger and BTB domain containing 18) in injured TG neurons following nerve injury. Restoring ZBTB18 expression alleviated nerve injury-induced mechanical allodynia, whereas its knockdown in intact TGs produces neuropathic pain symptoms.

Mechanistically, ZBTB18 transcriptionally represses Clic1 by binding to a specific cis-acting silencer within the Clic1 promoter region; disruption of this binding abolished both the suppression of CLIC1 and the associated antinociceptive effects. Furthermore, ZBTB18 recruits the NuRD (nucleosome remodeling and deacetylase) complex through direct interaction between its BTB domain and CHD4. Dysfunction of this recruitment attenuates histone H3K27ac deacetylation, and enhances RNA polymerase II enrichment at the Clic1 promoter, thereby facilitating Clic1 transcription.