{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:07:25Z","timestamp":1791130045781,"version":"4.1.0"},"reference-count":22,"publisher":"National Academy of Sciences","issue":"4","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,2,17]]},"abstract":"<jats:p>\n                    The circadian hormone melatonin is synthesized predominantly in the pineal gland by the actions of two pineal-specific enzymes: serotonin\n                    <jats:italic>N<\/jats:italic>\n                    -acetyltransferase (NAT) and hydroxyindole-\n                    <jats:italic>O<\/jats:italic>\n                    -methyltransferase (HIOMT). Pineal night-specific ATPase (PINA), another pineal- and night-specific protein we recently identified, is produced as a truncated form of the Wilson disease gene (\n                    <jats:italic>Atp7b<\/jats:italic>\n                    ) product. To identify the regulatory elements required for pineal-specific gene expression, we isolated sequences upstream of the rat PINA gene and discovered a cis-acting element that is recognized by a novel pineal\/retina-specific nuclear factor. This pineal regulatory element (PIRE) has a consensus of TAATC\/T and is present in six copies in the 5\u2032 regulatory region of the PINA gene, at least three copies in the rat NAT promoter, and at least one copy in each of the putative HIOMT promoters A and B. A recently identified retina-specific protein, cone rod homeobox (CRX), binds to PIRE\n                    <jats:italic>in vitro<\/jats:italic>\n                    and transactivates PIRE-reporter constructs. These data suggest that\n                    <jats:italic>Crx<\/jats:italic>\n                    may play a crucial role in regulating pineal gene expression through interactions with PIRE.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.4.1876","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"1876-1881","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":90,"title":["A pineal regulatory element (PIRE) mediates transactivation by the pineal\/retina-specific transcription factor CRX"],"prefix":"10.1073","volume":"95","author":[{"given":"Xiaodong","family":"Li","sequence":"first","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"Zack","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solomon H.","family":"Snyder","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimo","family":"Borjigin","sequence":"additional","affiliation":[{"name":"Departments of Neuroscience, Pharmacology and Molecular Science, Psychiatry, and Molecular Biology and Genetics and Wilmer Institute, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 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