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Bioinformatics Advance Access published online on January 15, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp031
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A new cis-acting regulatory element driving gene expression in the zebrafish pineal gland

Shahar Alon 1, Eli Eisenberg 2,*, Jasmine Jacob-Hirsch 3, Gideon Rechavi 3, Gad Vatine 1, Reiko Toyama 4, Steve L. Coon 5, David C. Klein 5 and Yoav Gothilf 1,*

1Department of Neurobiology, The George S. Wise Faculty of Life Sciences and 2Raymond and Beverly Sackler School of Physics and Astronomy, Tel Aviv University, Tel Aviv 69978, Israel. 3Cancer Research Center, Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Israel. 4Laboratory of Molecular Genetics and 5Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

*To whom correspondence should be addressed. Eli Eisenberg and Yoav Gothilf; E-mail: yoavg{at}tauex.tau.ac.il; elieis{at}post.tau.ac.il


  Abstract

Motivation: The identification of functional cis-acting DNA regulatory elements is a crucial step towards understanding gene regulation. Ab initio motif detection algorithms have been extensively used in search of regulatory elements. Yet, their success in providing experimentally validated regulatory elements in vertebrates has been limited.

Results: Here we report in-silico identification and in-vivo validation of regulatory elements that determine enhanced gene expression in the pineal gland of zebrafish. Microarray data enabled detection of genes that exhibit high expression in the pineal gland. The promoter regions of these genes were computationally analyzed in order to identify over-represented motifs. The highest ranking motif identified is a CRX/OTX binding site, known to govern expression in the pineal gland and retina. The second highest ranking motif was not reported before; we experimentally validated its function in-vivo by mutational analysis. The methodology presented here may be applicable as a general scheme for finding regulatory elements that contribute to tissue-specific gene expression.

Availability: http://odin.mdacc.tmc.edu/jhu/lysatearray-analysis/.

Contacts: yoavg{at}tauex.tau.ac.il; elieis{at}post.tau.ac.il

Associate Editor: Prof. Alfonso Valencia

Received on November 1, 2008; revised on December 21, 2008; accepted on January 8, 2009

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