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J. Biol. Chem., Vol. 283, Issue 16, 10881-10891, April 18, 2008

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A Novel, Evolutionarily Conserved Enhancer of Cone Photoreceptor-specific Expression^*

From the School of Biomolecular & Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland

The subunit of cone transducin (TC) is expressed exclusively in cone photoreceptors of the eye and pineal. TCisakey phototransduction protein, and inherited mutations in TC cause total color blindness in humans. We use transgenic zebrafish to identify and characterize cone photoreceptor regulatory element 1 (CPRE-1) a novel 20-bp enhancer element in the TC promoter (TCP). CPRE-1 is located 2.5 kb upstream of the translation start site and is necessary for strong cone photoreceptor-specific expression in vivo. CPRE-1 comprises of a modular arrangement of two 10-bp elements that have separate, but co-dependent transcriptional activities. In vitro, CPRE-1 specifically binds nuclear factors that are enriched in ocular tissue. Bioinformatic alignments reveal that CPRE-1 sites are evolutionarily conserved in the promoter regions of fish, rodent, and mammalian TC orthologues and identify a 5'-CTGGAGTG(A/T)TGGA(G/A)GCAGGG(G/C)T-3' consensus sequence.

Received for publication, December 21, 2007 , and in revised form, February 11, 2008.

^* This work was supported in part by Science Foundation Ireland Research Frontiers Program 2005-2008 (Grant 05/RFP/Gen0027), Science Foundation Ireland Investigator Grant Award (Grant 04/IN3/B559), and University College Dublin Presidents Award 2003-2005. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1.

¹ Supported by under the Science Foundation Ireland UREKA (Undergraduate Research Experience & Knowledge Award) program.

² To whom correspondence should be addressed: Tel.: 353-1-716-6740; Fax: 353-1-283-7211; E-mail: brendan.kennedy{at}ucd.ie.

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