Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear.
Differential regulation of mammalian and avian ATOH1 by E2F1 and its implication for hair cell regeneration in the inner ear.
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DOI：
10.1038/s41598-021-98816-w
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发表时间：
2021-09-29
影响因子：
4.6
通讯作者：
Dawson SJ
中科院分区：
文献类型：
--
作者：
Gómez-Dorado M;Daudet N;Gale JE;Dawson SJ
哺乳动物内耳再生其机械感觉毛细胞的能力有限。这种再生能力的缺乏是人类与年龄相关的听力损失的高发病率的基础。相比之下，非哺乳类脊椎动物在损伤发生时可以形成新的毛细胞，这一机制取决于毛细胞前转录因子Atoh1表达的重新激活。在这里，我们表明，E2F转录因子家族的成员，已知在细胞周期进程中发挥关键作用，调节Atoh1的表达。E2F1通过与禽Atoh1基因远端的顺式调控区直接相互作用来激活鸡Atoh1。E2F不激活小鼠Atoh1基因表达，因为这种调控元件在哺乳动物中不存在。我们还表明，E2F1的表达动态变化在鸡听觉上皮耳毒性损伤和毛细胞再生。因此，我们提出了一种模型，其中非哺乳动物毛细胞的有丝分裂再生是由于E2F1介导的Atoh1表达的激活，这是一种在哺乳动物中已经丢失的机制。
The mammalian inner ear has a limited capacity to regenerate its mechanosensory hair cells. This lack of regenerative capacity underlies the high incidence of age-related hearing loss in humans. In contrast, non-mammalian vertebrates can form new hair cells when damage occurs, a mechanism that depends on re-activation of expression of the pro-hair cell transcription factor Atoh1. Here, we show that members of the E2F transcription factor family, known to play a key role in cell cycle progression, regulate the expression of Atoh1. E2F1 activates chicken Atoh1 by directly interacting with a cis-regulatory region distal to the avian Atoh1 gene. E2F does not activate mouse Atoh1 gene expression, since this regulatory element is absent in mammals. We also show that E2F1 expression changes dynamically in the chicken auditory epithelium during ototoxic damage and hair cell regeneration. Therefore, we propose a model in which the mitotic regeneration of non-mammalian hair cells is due to E2F1-mediated activation of Atoh1 expression, a mechanism which has been lost in mammals.
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影响因子：
4.6
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通讯作者：
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