Human Molecular Genetics Advance Access published online on March 17, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh117
© 2004 by Oxford University Press
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1 Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287
* To whom correspondence should be addressed. E-mail: dzack{at}bs.jhmi.edu.
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 5.8kb 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.
Article
QRX, a Novel Homeobox Gene, Modulates Photoreceptor Gene Expression
2 Department of Ophthalmology and Visual Science, Washington University School of Medicine, St. Louis, MO 63110
3 Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21287
4 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105; Current Address: National Brain Research Center, Gurgaon, India-122001
5 Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, IA 52242
6 Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287
7 Jules Stein Eye Institute, University of California-Los Angeles School of Medicine, Los Angeles, CA 90095
8 Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19014
9 Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48105
10 Program in Human Genetics and Molecular Biology, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Maumenee Bldg 809, 600 N. Wolfe St. Baltimore, MD 21287; Department of Ophthalmology, Johns Hopkins University School of Medicine, Maumenee Bldg 809, 600 N. Wolfe St. Baltimore, MD 21287; Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Maumenee Bldg 809, 600 N. Wolfe St. Baltimore, MD 21287; Department of Neuroscience, Johns Hopkins University School of Medicine, Maumenee Bldg 809, 600 N. Wolfe St. Baltimore, MD 21287
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