This Article Full Text Full Text (PDF) Supplemental Data Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager NURSA Molecule Pages Link Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nishio, S.-i. Articles by Laudet, V. Search for Related Content PubMed PubMed Citation Articles by Nishio, S.-i. Articles by Laudet, V.

OTX5 Regulates Pineal Expression of the Zebrafish REV-ERB through a New DNA Binding Site

Université de Lyon, Institut de Génomique Fonctionnelle de Lyon, Unité Mixte de Recherche 5242 du Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France

Address all correspondence and requests for reprints to: Vincent Laudet, Institut de Génomique Fonctionnelle de Lyon, Unité Mixte de Recherche 5242 du Centre National de la Recherche Scientifique, Université de Lyon, Institut National de la Recherche Agronomique, Institut Fédératif de Recherche 128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France. E-mail: vlaudet{at}ens-lyon.fr.

The pineal gland plays a central role in the photoneuroendocrine system and acts as a photosensory organ in lower vertebrates. The orphan nuclear receptor Rev-erb (NR1D1) has previously been shown to be expressed in the pineal and to be regulated with a robust circadian rhythm during zebrafish embryogenesis. This early pineal expression is under the control of the transcription factor Orthodenticle homeobox 5 (Otx5). In this paper, we show that Otx5 regulates the second zfRev-erb promoter, ZfP2. Despite the absence of a classical Otx-binding site within ZfP2, this regulation depends on the integrity of the Otx5 homeodomain. Mapping experiments as well as EMSAs show that this interaction between Otx5 and ZfP2 depends on a noncanonical bipartite Otx-binding site (GANNCTTA and TAAA) that we called pineal expression related element (PERE). We showed that PERE is necessary for pineal expression in vivo by injecting zebrafish embryos with wild type and mutated versions of zfRev-erb promoter fused to green fluorescent protein. Interestingly, PERE is found upstream of other genes expressed in the pineal gland, suggesting that it may play an important role in governing pineal expression. Our data establish that PERE is a novel cis-acting element contributing to pineal-specific gene expression and to Otx target gene regulation.

NURSA Molecule Pages Link:

Nuclear Receptors:   REV-ERBα