2. Academic Validation
  3. Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

  • Front Mol Neurosci. 2017 Mar 13;10:51. doi: 10.3389/fnmol.2017.00051.
Beier Bao 1,  Yingzi He 2,  Dongmei Tang 2,  Wenyan Li 2,  Huawei Li 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Medical Neurobiology, Medical College of Fudan University Shanghai, China.
  • 2 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.
  • 3 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.
PMID: 28348517 DOI: 10.3389/fnmol.2017.00051
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 an in vivo animal 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 of p21 and p27 in 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.

Keywords

GSK-J4; H3K27 demethylation; hair cell; regeneration; zebrafish.

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