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

In this study, we investigated the effect of G9a (KMT1C, EHMT2), a major histone lysine methyltransferase encoded by the humanEHMT2 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...

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