Circadian regulation of low density lipoprotein receptor promoter activity by CLOCK/BMAL1, Hes1 and Hes6

LDLR mRNA oscillates in the liver in a functional clock-dependent manner.

• Blood glucose, plasma triglyceride, and cholesterol levels vary distinctly throughout the day in mice.
• Three potential E-box sequences identified in the human LDLR promoter suggest regulation by specific transcription factors.
• The CLOCK/BMAL1 complex is associated with the upregulation of LDLR promoter activity regardless of serum levels.
• Hes1 and Hes6 can downregulate LDLR expression, but this effect is only observed in serum-depleted conditions.
• Hes6 and Hes1 mRNA levels oscillate in an anti-phasic manner in wild-type mice but not in per1-/-per2-/- mice.
• Conservation of three E-boxes among mouse, rat, and human hes6 genes indicates a similar regulatory mechanism across species.

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