{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:08:14Z","timestamp":1790381294597,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,11,26]]},"abstract":"<jats:p>\n                    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 (\n                    <jats:italic>exorh<\/jats:italic>\n                    ) 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\n                    <jats:italic>exorh<\/jats:italic>\n                    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\n                    <jats:italic>exorh<\/jats:italic>\n                    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 (\n                    <jats:italic>rh<\/jats:italic>\n                    ) promoter that drives retina-specific expression, we created a reporter construct having ectopic PIPE in the\n                    <jats:italic>rh<\/jats:italic>\n                    promoter at a position equivalent to that in the\n                    <jats:italic>exorh<\/jats:italic>\n                    promoter by introducing five nucleotide changes. Such a slight modification in the\n                    <jats:italic>rh<\/jats:italic>\n                    promoter induced ectopic enhanced green fluorescent protein expression in the pineal gland without affecting its retinal expression. These results identify PIPE as a critical\n                    <jats:italic>cis<\/jats:italic>\n                    -element contributing to the pineal-specific gene expression, in combination with the Crx\/Otx-binding site(s).\n                  <\/jats:p>","DOI":"10.1073\/pnas.232444199","type":"journal-article","created":{"date-parts":[[2002,11,26]],"date-time":"2002-11-26T12:42:52Z","timestamp":1038314572000},"page":"15456-15461","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":49,"title":["Pineal expression-promoting element (PIPE), a\n                    <i>cis-<\/i>\n                    acting element, directs pineal-specific gene expression in zebrafish"],"prefix":"10.1073","volume":"99","author":[{"given":"Yoichi","family":"Asaoka","sequence":"first","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan Asia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mano","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan Asia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan Asia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Fukada","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan Asia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,11,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1981.46.5.1018"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1001650205"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00612489"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.52.Suppl_441"},{"key":"e_1_3_3_5_2","first-page":"625","volume":"33","author":"Shedpure M.","year":"1995","unstructured":"Shedpure M. & Pati, A. 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