Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes
Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes
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DOI：
10.1016/s0896-6273(00)80394-3
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发表时间：
1997-11-01
期刊：
影响因子：
16.2
通讯作者：
Zack, DJ
中科院分区：
文献类型：
--
作者：
Chen, SM;Wang, QL;Zack, DJ
OTD/OTX基因家族编码成对的类同源域蛋白，参与调节前头结构和感觉器官发育。利用含有牛视紫红质启动子Ret 4位点的酵母单杂交筛选，我们克隆了该家族的一个新成员CRX(Cone Rod Homeobox)。CRX编码一个299个氨基酸残基的蛋白，在其N端附近有一个成对的同源结构域。在成年，它主要在光感受器和松果体细胞中表达。在发育中的小鼠视网膜中，它在胚胎第12.5天(E12.5)表达。重组CRX在体外不仅与Ret 4结合，而且还与Ret 1和BAT-1结合。在瞬时转基因研究中，CRX反式激活视紫红质启动子-报告结构。它的活性与NR1具有协同作用。CRX还结合和反式激活其他几种光感受器细胞特异性蛋白的基因(光感受器间类视黄素结合蛋白、β-磷酸二酯酶和arrestin)。人类CRX定位于19q13.3，视锥细胞杆状营养不良(CORDII)的位置。这些研究表明，CRX可能是感光细胞发育和基因表达的重要调节因子，也是CORDII和其他视网膜疾病的候选基因。
The otd/Otx gene family encodes paired-like homeodomain proteins that are involved in the regulation of anterior head structure and sensory organ development. Using the yeast one-hybrid screen with a bait containing the Ret 4 site from the bovine rhodopsin promoter, we have cloned a new member of the family, Crx (Cone rod homeobox). Crx encodes a 299 amino acid residue protein with a paired-like homeodomain near its N terminus. In the adult, it is expressed predominantly in photoreceptors and pinealocytes. In the developing mouse retina, it is expressed by embryonic day 12.5 (E12.5). Recombinant Crx binds in vitro not only to the Ret 4 site but also to the Ret 1 and BAT-1 sites. In transient transfection studies, Crx transactivates rhodopsin promoter-reporter constructs. Its activity is synergistic with that of Nr1. Crx also binds to and transactivates the genes for several other photoreceptor cell-specific proteins (interphotoreceptor retinoid-binding protein, beta-phosphodiesterase, and arrestin). Human Crx maps to chromosome 19q13.3, the site of a cone rod dystrophy (CORDII). These studies implicate Crx as a potentially important regulator of photoreceptor cell development and gene expression and also identify it as a candidate gene for CORDII and other retinal diseases.