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journal article·2022-04Open access

Cdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons

Zhao‐Wei Sun, Jarod M. Waybright, Serap Beldar, Lu Chen, Caroline A. Foley, Jacqueline L. Norris‐Drouin, Tian‐Jie Lyu, Aiping Dong, Jinrong Min, Yu‐Pu Wang, Lindsey I. James, Yun Wang

Advanced Science· Volume 9· Issue 10
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Abstract

Abstract 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 (Kv) subfamily member Kv2.1 transcription. Loss function of CDYL enhances total Kv and Kv2.1 current density in dorsal root ganglia and knockdown of Kv2.1 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.
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Research context

Materials processing

OpenAlex topics: Pain Mechanisms and Treatments · Cholinesterase and Neurodegenerative Diseases · Pharmacological Receptor Mechanisms and Effects

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Neuroscience Research Institute and Department of Neurobiology School of Basic Medical Sciences Key Laboratory for Neuroscience Ministry of Education/National Health Commission and State Key Laboratory of Natural and Biomimetic Drugs Peking University Beijing 100083 China

Institute of Military Cognitive and Brain Sciences Academy of Military Medical Sciences Beijing 100039 China

Center for Integrative Chemical Biology and Drug Discovery Division of Chemical Biology and Medicinal Chemistry UNC Eshelman School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill NC 27599 USA

Structural Genomics Consortium University of Toronto 101 College Street Toronto Ontario M5G 1L7 Canada

Hubei Key Laboratory of Genetic Regulation and Integrative Biology School of Life Sciences Central China Normal University Wuhan Hubei 430079 China

Department of Physiology University of Toronto Toronto Ontario M5S 1A8 Canada

PKU‐IDG/McGovern Institute for Brain Research Peking University Beijing 100871 China

Funding

National Natural Science Foundation of China · National Institute on Drug Abuse

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