Open AccessCdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons
Author(s) -
Sun ZhaoWei,
Waybright Jarod M.,
Beldar Serap,
Chen Lu,
Foley Caroline A.,
NorrisDrouin Jacqueline L.,
Lyu TianJie,
Dong Aiping,
Min Jinrong,
Wang YuPu,
James Lindsey I.,
Wang Yun
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202104317
Subject(s) - epigenetics , neuropathic pain , nociception , chromodomain , neuroscience , gene knockdown , nociceptor , sensory system , transcription factor , gene silencing , histone , biology , microbiology and biotechnology , genetics , receptor , rna , gene , helicase
Epigenetic modifications are involved in the onset, development, and maintenance of pain; however, the precise epigenetic mechanism underlying pain regulation remains elusive. Here it is reported that the epigenetic factor chromodomain Y‐like (CDYL) is crucial for pain processing. Selective knockout of CDYL in sensory neurons results in decreased neuronal excitability and nociception. Moreover, CDYL facilitates histone 3 lysine 27 trimethylation (H3K27me3) deposition at the Kcnb1 intron region thus silencing voltage‐gated potassium channel (K v ) subfamily member K v 2.1 transcription. Loss function of CDYL enhances total K v and K v 2.1 current density in dorsal root ganglia and knockdown of K v 2.1 reverses the pain‐related phenotypes of Cdyl deficiency mice. Furthermore, focal administration of a novel potent CDYL antagonist blunts nociception and attenuates neuropathic pain. These findings reveal that CDYL is a critical regulator of pain sensation and shed light on the development of novel analgesics targeting epigenetic mechanisms.