Pineal expression-promoting element (PIPE), a cis-acting element, directs pineal-specific gene expression in zebrafish

Yoichi Asaoka, Hiroaki Mano, Daisuke Kojima, Yoshitaka Fukada*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


The pineal gland, sharing morphological and biochemical similarities with the retina, plays a unique and central role in the photoneuroendocrine system. The unique development of the pineal gland is directed by a specific combination of the expressed genes, but little is known about the regulatory mechanism underlying the pineal-specific gene expression. We isolated a 1.1-kbp fragment upstream of the zebrafish exo-rhodopsin (exorh) gene, which is expressed specifically in the pineal gland. Transgenic analysis using an enhanced green fluorescent protein reporter gene demonstrated that the proximal 147-bp region of the exorh promoter is sufficient to direct pineal-specific expression. This region contains three copies of a putative cone rod homeobox (Crx)/Otx-binding site, which is known to be required for expression of both retina- and pineal-specific genes. Deletion and mutational analyses of the exorh promoter revealed that a previously uncharacterized sequence TGACCCCAATCT termed pineal expression-promoting element (PIPE) is required for pineal-specific promoter activity in addition to the Crx/Otx-binding sites. By using the zebrafish rhodopsin (rh) promoter that drives retina-specific expression, we created a reporter construct having ectopic PIPE in the rh promoter at a position equivalent to that in the exorh promoter by introducing five nucleotide changes. Such a slight modification in the rh promoter induced ectopic enhanced green fluorescent protein expression in the pineal gland without affecting its retinal expression. These results identify PIPE as a critical cis-element contributing tothe pineal-specific gene expression, in combination with the Crx/Otx-binding site(s).

Original languageEnglish
Pages (from-to)15456-15461
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
Publication statusPublished - 2002 Nov 26

ASJC Scopus subject areas

  • General


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