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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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Oiwa A,Kakizawa T,Miyamoto T,Yamashita K,Jiang W,Takeda T,Suzuki S,Hashizume K

doi

10.1016/j.bbrc.2006.12.131

subject

Has Abstract

pub_date

2007-02-23 00:00:00

pages

895-901

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)02757-4

journal_volume

353

pub_type

杂志文章

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