生物钟基因 Bmal1 控制甲状腺激素介导的光谱特征和视锥光感受器功能。
The Circadian Clock Gene Bmal1 Controls Thyroid Hormone-Mediated Spectral Identity and Cone Photoreceptor Function.
机构信息
Department of Ophthalmic Research, Cole Eye Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
出版信息
Cell Rep. 2017 Oct 17;21(3):692-706. doi: 10.1016/j.celrep.2017.09.069.
Circadian clocks regulate various aspects of photoreceptor physiology, but their contribution to photoreceptor development and function is unclear. Cone photoreceptors are critical for color vision. Here, we define the molecular function of circadian activity within cone photoreceptors and reveal a role for the clock genes Bmal1 and Per2 in regulating cone spectral identity. ChIP analysis revealed that BMAL1 binds to the promoter region of the thyroid hormone (TH)-activating enzyme type 2 iodothyronine deiodinase (Dio2) and thus regulates the expression of Dio2. TH treatment resulted in a partial rescue of the phenotype caused by the loss of Bmal1, thus revealing a functional relationship between Bmal1 and Dio2 in establishing cone photoreceptor identity. Furthermore, Bmal1 and Dio2 are required to maintain cone photoreceptor functional integrity. Overall, our results suggest a mechanism by which circadian proteins can locally regulate the availability of TH and influence tissue development and function.
昼夜节律钟调节视锥细胞生理学的各个方面，但它们对视锥细胞发育和功能的贡献尚不清楚。视锥细胞对于色觉至关重要。在这里，我们定义了昼夜节律活动在视锥细胞中的分子功能，并揭示了时钟基因 Bmal1 和 Per2 在调节视锥细胞光谱特征中的作用。ChIP 分析显示，BMAL1 结合到甲状腺激素 (TH) 激活酶 2 碘甲状腺原氨酸脱碘酶 (Dio2) 的启动子区域，从而调节 Dio2 的表达。TH 处理导致由 Bmal1 缺失引起的表型部分恢复，从而揭示了 Bmal1 和 Dio2 在建立视锥细胞特征中的功能关系。此外，Bmal1 和 Dio2 对于维持视锥细胞功能完整性是必需的。总的来说，我们的结果表明了昼夜节律蛋白可以局部调节 TH 的可用性并影响组织发育和功能的机制。
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