{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:45:21Z","timestamp":1781109921310,"version":"3.54.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,3,22]]},"abstract":"<jats:p>\n                    The circadian clock is phase-delayed or -advanced by light when given at early or late subjective night, respectively. Despite the importance of the time-of-day\u2013dependent phase responses to light, the underlying molecular mechanism is poorly understood. Here, we performed a comprehensive analysis of light-inducible genes in the chicken pineal gland, which consists of light-sensitive clock cells representing a prototype of the clock system. Light stimulated expression of 62 genes and 40 ESTs by &gt;2.5-fold, among which genes responsive to the heat shock and endoplasmic reticulum stress as well as their regulatory transcription factors heat shock factor (HSF)1, HSF2, and X-box-binding protein 1 (XBP1) were strongly activated when a light pulse was given at late subjective night. In contrast, the light pulse at early subjective night caused prominent induction of\n                    <jats:italic>E4bp4<\/jats:italic>\n                    , a key regulator in the phase-delaying mechanism of the pineal clock, along with activation of a large group of cholesterol biosynthetic genes that are targets of sterol regulatory element-binding protein (SREBP) transcription factor. We found that the light pulse stimulated proteolytic formation of active SREBP-1 that, in turn, transactivated\n                    <jats:italic>E4bp4<\/jats:italic>\n                    expression, linking SREBP with the light-input pathway of the pineal clock. As an output of light activation of cholesterol biosynthetic genes, we found light-stimulated pineal production of a neurosteroid, 7\u03b1-hydroxypregnenolone, demonstrating a unique endocrine function of the pineal gland. Intracerebroventricular injection of 7\u03b1-hydroxypregnenolone activated locomotor activities of chicks. Our study on the genome-wide gene expression analysis revealed time-of-day\u2013dependent light activation of signaling pathways and provided molecular connection between gene expression and behavior through neurosteroid release from the pineal gland.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1015959108","type":"journal-article","created":{"date-parts":[[2011,3,8]],"date-time":"2011-03-08T07:01:21Z","timestamp":1299567681000},"page":"4864-4869","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways"],"prefix":"10.1073","volume":"108","author":[{"given":"Megumi","family":"Hatori","sequence":"first","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiko","family":"Iitsuka","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiro","family":"Kurabayashi","sequence":"additional","affiliation":[{"name":"Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Haraguchi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Education and Integrated Arts and Sciences, Waseda University, Tokyo 162-8480, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kokame","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Nakai","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Yamaguchi University School of Medicine, Yamaguchi 755-8505, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyuki","family":"Miyata","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Osaka 565-8565, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyoshi","family":"Tsutsui","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Education and Integrated Arts and Sciences, Waseda University, Tokyo 162-8480, Japan;"}],"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, Tokyo 113-0033, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,3,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0092-8674(00)80566-8","article-title":"Molecular bases for circadian clocks","volume":"96","author":"Dunlap JC","year":"1999","unstructured":"JC Dunlap, Molecular bases for circadian clocks. 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