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Human Molecular Genetics Advance Access originally published online on March 17, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 10 1025-1040
DOI: 10.1093/hmg/ddh117
Human Molecular Genetics, Vol. 13, No. 10 © Oxford University Press 2004; all rights reserved

QRX, a novel homeobox gene, modulates photoreceptor gene expression

Qing-liang Wang1,2, Shiming Chen5, Noriko Esumi2, Prabodh K. Swain6,{dagger}, Heidi S. Haines8, Guanghua Peng5, B. Michele Melia2, Iain McIntosh1, John R. Heckenlively9, Samuel G. Jacobson10, Edwin M. Stone8, Anand Swaroop6,7 and Donald J. Zack1,2,3,4,*

1Program in Human Genetics and Molecular Biology, McKusick–Nathans Institute of Genetic Medicine, 2Department of Ophthalmology, 3Department of Molecular Biology and Genetics, 4Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, 5Department of Ophthalmology and Visual Science, Washington University School of Medicine, St Louis, MO, USA, 6Department of Ophthalmology and Visual Sciences and 7Human Genetics, University of Michigan, Ann Arbor, MI, USA, 8Department of Ophthalmology, University of Iowa College of Medicine, Iowa City, IA, USA, 9Jules Stein Eye Institute, University of California–Los Angeles School of Medicine, Los Angeles, CA, USA and 10Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA

Received January 8, 2004; Accepted March 10, 2004

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.

* To whom correspondence should be addressed at: Johns Hopkins University School of Medicine, Maumenee Bldg 809, 600 N. Wolfe St, Baltimore, MD 21287, USA. Tel: +1 4105025230; Fax: +1 4105025382; Email: dzack{at}bs.jhmi.edu


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