title: Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts.
abstract: The H3K27 demethylases are involved in a variety of biological processes, including cell differentiation, proliferation, and cell death by regulating transcriptional activity. However, the function of H3K27 demethylation in the field of hearing research is poorly understood. Here, we investigated the role of H3K27me3 histone demethylase activity in hair cell regeneration using anin vivoanimal model. Our data showed that pharmacologic inhibition of H3K27 demethylase activity with the specific small-molecule inhibitor GSK-J4 decreased the number of regenerated hair cells in response to neomycin damage. Furthermore, inhibition of H3K27me3 histone demethylase activity dramatically suppressed cell proliferation and activated caspase-3 levels in the regenerating neuromasts of the zebrafish lateral line. GSK-J4 administration also increased the expression ofp21andp27in neuromast cells and inhibited the ERK signaling pathway. Collectively, our findings indicate that H3K27me3 demethylation is a key epigenetic regulator in the process of hair cell regeneration in zebrafish and suggest that H3K27me3 histone demethylase activity might be a novel therapeutic target for the treatment of hearing loss.
authors.affiliation: State Key Laboratory of Medical Neurobiology, Medical College of Fudan University Shanghai, China.
authors.forename: Beier
authors.initials: B
authors.lastname: Bao
authors.affiliation: ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, China; Key Laboratory of Hearing Medicine of National Health and Family Planning CommissionShanghai, China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: He
authors.affiliation: ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, China; Key Laboratory of Hearing Medicine of National Health and Family Planning CommissionShanghai, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Tang
authors.affiliation: ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, China; Key Laboratory of Hearing Medicine of National Health and Family Planning CommissionShanghai, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Neurobiology, Medical College of Fudan UniversityShanghai, China; ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan UniversityShanghai, China; Key Laboratory of Hearing Medicine of National Health and Family Planning CommissionShanghai, China; Institutes of Biomedical Science, Fudan UniversityShanghai, China; The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan UniversityShanghai, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Li
keywords: GSK-J4; H3K27 demethylation; hair cell; regeneration; zebrafish