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

Mouse SHP mRNA exhibited a circadian expression pattern in the liver.

• CLOCK-BMAL1, essential components of the circadian clock, bound to the E-box in the mSHP promoter and increased its activity by 4-fold.
• LRH-1 stimulated the mSHP promoter, with CLOCK-BMAL1 enhancing this effect.
• SHP repressed the combined activation of the mSHP promoter by CLOCK-BMAL1 and LRH-1.
• Direct protein-protein interactions were observed between LRH-1 and CLOCK.
• The cyclic expression of mSHP may influence the daily activity of other nuclear receptors and support circadian liver functions.

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