Multiple Mechanisms Regulate Circadian Expression of the Gene for Cholesterol 7α-Hydroxylase (Cyp7a), a Key Enzyme in Hepatic Bile Acid Biosynthesis

The expression profile of the Cyp7a transcript in wild-type mice shows a strong circadian rhythm.

• Cyp7a exhibits a robust circadian expression pattern in the liver of wild-type mice under both light-dark cycles and constant darkness.
• In Clock/Clock mice, Cyp7a expression maintains a circadian rhythm at an enhanced level but with a lower amplitude and becomes arrhythmic at the protein level.
• Cyp8b mRNA expression in wild-type mice displays a shifted circadian rhythm and becomes arrhythmic in Clock/Clock mice, while remaining at levels similar to wild-type.
• Hmgcr mRNA loses its strong circadian rhythm in Clock/Clock mice and shows expression levels comparable to wild-type.
• Key regulators of Cyp7a expression, such as Dbp and Rev-erb, are disrupted in Clock/Clock mice, while some other regulators show either less impact or enhanced expression.
• Transcription factors like REV-ERBalpha/beta, DBP, and LXRalpha enhance Cyp7a promoter activity, indicating their role in its circadian regulation.

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