QRX, a novel homeobox gene, modulates photoreceptor gene expression
QRX, a novel homeobox gene, modulates photoreceptor gene expression
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DOI：
10.1093/hmg/ddh117
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发表时间：
2004-05-15
影响因子：
3.5
通讯作者：
Zack, DJ
中科院分区：
文献类型：
--
作者：
Wang, QL;Chen, SM;Zack, DJ
以牛视紫红质启动子Ret-1的DNA调控元件为诱饵，通过酵母单杂交筛选，获得了一个新的类配对同源盒基因QRQ 1。视网膜色素瘤优先在视网膜的外核层和内核层中表达。它的同源结构域几乎与Rx/Rax相同，Rx/Rax是一种对眼睛发育至关重要的转录因子，但它在其他地方仅具有有限的同源性。虽然Qcnt和Rx/Rax在体外显示出相似的DNA结合特性，但这两种蛋白质在启动子活性测定中表现出不同的靶标选择性和功能行为。QRX协同增加感光细胞转录因子Crx和NRL的反式激活功能，并与CRX发生物理相互作用。牛和人类的基因组中存在着辅酶Q1，但小鼠的基因组中似乎没有。尽管如此，人QRX的5.8kb上游区域能够指导转基因小鼠中推定的感光前体细胞中的表达。这些结果表明，QR 41可能参与调节感光细胞基因的表达。此外，在三名视网膜变性患者中发现罕见的杂合QRX序列变化，这提高了QRX可能参与疾病发病机制的可能性。
A novel paired-like homeobox gene, designated as Qrx, was identified by a yeast one-hybrid screen using the bovine Rhodopsin promoter Ret-1 DNA regulatory element as bait. Qrx is preferentially expressed in both the outer and inner nuclear layers of the retina. Its homeodomain is nearly identical to that of Rx/Rax, a transcription factor that is essential for eye development, but it shares only limited homology elsewhere. Although Qrx and Rx/Rax show similar DNA binding properties in vitro, the two proteins demonstrate distinct target selectivity and functional behavior in promoter activity assays. QRX synergistically increases the transactivating function of the photoreceptor transcription factors Crx and NRL and it physically interacts with CRX. Qrx is present in the bovine and human genomes, but appears to be absent from the mouse genome. Nonetheless, a 5.8 kb upstream region of human QRX is capable of directing expression in presumptive photoreceptor precursor cells in transgenic mice. These results indicate that Qrx may be involved in modulating photoreceptor gene expression. In addition, the finding of rare heterozygous QRX sequence changes in three individuals with retinal degeneration raises the possibility that QRX may be involved in disease pathogenesis.