skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1

Abstract

Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as a repressor for wide variety of nuclear hormone receptors. We demonstrated here that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian clock components, bound to E-box (CACGTG), and stimulated the promoter activity by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated promoter activity, but strongly repressed the synergistic activation of CLOCK-BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of direct protein-protein interaction between LRH-1 and CLOCK. In summary, this study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene to generate the circadian oscillation. The cyclic expression of mSHP may affect daily activity of other nuclear receptors and contribute to circadian liver functions.

Authors:
 [1];  [2];  [1];  [1];  [3];  [1];  [1];  [1]
  1. Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan)
  2. Shinshu University Graduate School of Medicine, Institute on Aging and Adaptation, Department of Aging Medicine and Geriatrics, Matsumoto 390-8621 (Japan). E-mail: tkaki@hsp.md.shinshu-u.ac.jp
  3. Department of Endocrinology, First Clinical College, Harbin Medical University, 150001 (China)
Publication Date:
OSTI Identifier:
20979805
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 353; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2006.12.131; PII: S0006-291X(06)02757-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; GENE REGULATION; HORMONES; IN VITRO; LIVER; MICE; RECEPTORS

Citation Formats

Oiwa, Ako, Kakizawa, Tomoko, Miyamoto, Takahide, Yamashita, Koh, Jiang, Wei, Takeda, Teiji, Suzuki, Satoru, and Hashizume, Kiyoshi. Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2006.12.131.
Oiwa, Ako, Kakizawa, Tomoko, Miyamoto, Takahide, Yamashita, Koh, Jiang, Wei, Takeda, Teiji, Suzuki, Satoru, & Hashizume, Kiyoshi. Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1. United States. doi:10.1016/j.bbrc.2006.12.131.
Oiwa, Ako, Kakizawa, Tomoko, Miyamoto, Takahide, Yamashita, Koh, Jiang, Wei, Takeda, Teiji, Suzuki, Satoru, and Hashizume, Kiyoshi. Fri . "Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1". United States. doi:10.1016/j.bbrc.2006.12.131.
@article{osti_20979805,
title = {Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1},
author = {Oiwa, Ako and Kakizawa, Tomoko and Miyamoto, Takahide and Yamashita, Koh and Jiang, Wei and Takeda, Teiji and Suzuki, Satoru and Hashizume, Kiyoshi},
abstractNote = {Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as a repressor for wide variety of nuclear hormone receptors. We demonstrated here that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian clock components, bound to E-box (CACGTG), and stimulated the promoter activity by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated promoter activity, but strongly repressed the synergistic activation of CLOCK-BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of direct protein-protein interaction between LRH-1 and CLOCK. In summary, this study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene to generate the circadian oscillation. The cyclic expression of mSHP may affect daily activity of other nuclear receptors and contribute to circadian liver functions.},
doi = {10.1016/j.bbrc.2006.12.131},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 353,
place = {United States},
year = {Fri Feb 23 00:00:00 EST 2007},
month = {Fri Feb 23 00:00:00 EST 2007}
}