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Journal of the Association for Research in Otolaryngology
Published in: Journal of the Association for Research in Otolaryngology 3/2019

01-06-2019 | Epigenetics | Research Article

Inhibition of Histone Methyltransferase G9a Attenuates Noise-Induced Cochlear Synaptopathy and Hearing Loss

Authors: Hao Xiong, Haishan Long, Song Pan, Ruosha Lai, Xianren Wang, Yuanping Zhu, Kayla Hill, Qiaojun Fang, Yiqing Zheng, Su-Hua Sha

Published in: Journal of the Association for Research in Otolaryngology | Issue 3/2019

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ABSTRACT

Posttranslational modification of histones alters their interaction with DNA and nuclear proteins, influencing gene expression and cell fate. In this study, we investigated the effect of G9a (KMT1C, EHMT2), a major histone lysine methyltransferase encoded by the human EHMT2 gene and responsible for histone H3 lysine 9 dimethylation (H3K9me2) on noise-induced permanent hearing loss (NIHL) in adult CBA/J mice. The conditions of noise exposure used in this study led to losses of cochlear synapses and outer hair cells (OHCs) and permanent auditory threshold shifts. Inhibition of G9a with its specific inhibitor BIX 01294 or with siRNA significantly attenuated these pathological features. Treatment with BIX 01294 also prevented the noise-induced decrease of KCNQ4 immunolabeling in OHCs. Additionally, G9a was increased in cochlear cells, including both outer and inner sensory hair cells, some spiral ganglion neurons (SGNs), and marginal cells, 1 h after the completion of the noise exposure. Also subsequent to noise exposure, immunoreactivity for H3K9me2 appeared in some nuclei of OHCs following a high-to-low frequency gradient with more labeled OHCs in the 45-kHz than the 32-kHz region, as well as in the marginal cells and in some SGNs of the basal turn. These findings suggest that epigenetic modifications of H3K9me2 are involved in NIHL and that pharmacological targeting of G9a may offer a strategy for protection against cochlear synaptopathy and NIHL.
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Metadata
Title
Inhibition of Histone Methyltransferase G9a Attenuates Noise-Induced Cochlear Synaptopathy and Hearing Loss
Authors
Hao Xiong
Haishan Long
Song Pan
Ruosha Lai
Xianren Wang
Yuanping Zhu
Kayla Hill
Qiaojun Fang
Yiqing Zheng
Su-Hua Sha
Publication date
01-06-2019
Publisher
Springer US
Keyword
Epigenetics
Published in
Journal of the Association for Research in Otolaryngology / Issue 3/2019
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI
https://doi.org/10.1007/s10162-019-00714-6

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