The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes
The rod photoreceptor-specific nuclear receptor Nr2e3 represses transcription of multiple cone-specific genes
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DOI：
10.1523/jneurosci.3571-04.2005
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发表时间：
2005-01-05
影响因子：
5.3
通讯作者：
Nathans, J
中科院分区：
文献类型：
--
作者：
Chen, JC;Rattner, A;Nathans, J
这项研究解决了一个遗传调控机制，建立了不同的身份杆和锥光感受器。先前的研究表明，在人类或小鼠中，编码感光细胞特异性核受体Nr2e3的基因突变会导致以短波视锥细胞数量增加为特征的进行性视网膜变性。在目前的工作中，我们已经检查了哺乳动物和鱼类中Nr2e3蛋白定位的细胞和发育模式，使用与重组Nr2e3结合的循环鉴定了最佳Nr2e3 DNA结合位点，表征了野生型和转染细胞中Nr2e3中疾病相关点突变之一的转录活性，并表征了天然存在的Nr2e3突变体（rd7）小鼠中的转录缺陷。这些实验表明，在成熟的脊椎动物视网膜中，Nr2e3只在视杆中表达，Nr2e3的表达是视杆特异性光感受器发育途径中最早的事件之一，并且Nr2e3直接或间接地作为视杆光感受器细胞中视锥特异性基因的阻遏物起作用。
This study addresses one genetic regulatory mechanism that establishes the distinct identities of rod and cone photoreceptors. Previous work has shown that mutations in either humans or mice in the gene coding for photoreceptor-specific nuclear receptor Nr2e3 cause a progressive retinal degeneration characterized by increased numbers of short-wave cones. In the present work, we have examined the cellular and developmental pattern of Nr2e3 protein localization in mammals and fish, identified an optimal Nr2e3 DNA-binding site using cycles of binding to recombinant Nr2e3, characterized the transcriptional activity of wild type and one of the disease-associated point mutations in Nr2e3 in transfected cells, and characterized the transcriptional defects in the naturally occurring Nr2e3 mutant (rd7) mouse. These experiments indicate that in the mature vertebrate retina Nr2e3 is expressed exclusively in rods, that expression of Nr2e3 is one of the earliest events in the pathway of rod-specific photoreceptor development, and that Nr2e3 functions, either directly or indirectly, as a repressor of cone-specific genes in rod photoreceptor cells.