NDLI: Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways.

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Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways.

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Light-dependent and circadian clock-regulated activation of sterol regulatory element-binding protein, X-box-binding protein 1, and heat shock factor pathways.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Haraguchi, Shogo Hatori, Megumi Hirota, Tsuyoshi Iitsuka, Michiko Sato, Ryuichiro Tsutsui, Kazuyoshi Nakai, Akira Fukada, Yoshitaka Kurabayashi, Nobuhiro Kokame, Koichi Miyata, Toshiyuki
Description	Author Affiliation: Hatori M ( Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Tokyo 113-0033, Japan.);
Abstract	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-dependent 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 >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 E4bp4, 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 E4bp4 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 -hydroxypregnenolone, demonstrating a unique endocrine function of the pineal gland. Intracerebroventricular injection of 7 -hydroxypregnenolone activated locomotor activities of chicks. Our study on the genome-wide gene expression analysis revealed time-of-day-dependent light activation of signaling pathways and provided molecular connection between gene expression and behavior through neurosteroid release from the pineal gland.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	108
Language	English
Publisher	National Academy of Sciences
Publisher Date	2011-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Circadian Rhythm Physiology DNA-Binding Proteins Metabolism Gene Expression Regulation Heat-Shock Proteins Signal Transduction Sterol Regulatory Element Binding Protein 1 Transcription Factors 17-alpha-Hydroxypregnenolone Analogs & Derivatives Pharmacology Animals Behavior, Animal Drug Effects Radiation Effects Cholesterol Biosynthesis Endoplasmic Reticulum Genome-Wide Association Study Locomotion Molecular Sequence Data Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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