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.
复制标题
抑制 H3K27me3 组蛋白去甲基化酶活性可阻止斑马鱼侧线神经丘的增殖再生
DOI：
10.3389/fnmol.2017.00051
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发表时间：
2017
影响因子：
4.8
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Bao B;He Y;Tang D;Li W;Li H
H3K27去甲基酶通过调节转录活性参与多种生物学过程，包括细胞分化、增殖和细胞死亡。然而，H3K27去甲基化在听力研究领域的作用还知之甚少。在这里，我们使用活体动物模型研究了H3K27me3组蛋白去甲基酶活性在毛细胞再生中的作用。我们的数据显示，用特定的小分子抑制剂GSK-J4药物抑制H3K27去甲基酶的活性，可以减少对新霉素损伤的再生毛细胞的数量。此外，抑制H3K27me3组蛋白去甲基酶活性显著抑制斑马鱼侧线再生神经肥大细胞的增殖和激活caspase-3水平。GSK-J4还可上调神经肥大细胞p21和p27的表达，抑制ERK信号通路。综上所述，我们的研究结果表明，H3K27me3去甲基化是斑马鱼毛细胞再生过程中一个关键的表观遗传调节因子，并提示H3K27me3组蛋白去甲基酶活性可能成为治疗听力损失的新靶点。
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.