The Circadian Regulation of Presenilin‐2 Gene Expression

Abstract

Circadian rhythms are generated by a molecular clock composed of clock genes and their protein products. Other genes are regulated in a rhythmic way by this molecular clockwork, but are not themselves constituents of the clock. This study shows that one of these clock‐controlled genes encodes the signalling protein Presenilin‐2. Indeed, evidence is presented that the promoter of the mouse Presenilin‐2 gene is bound and activated by CLOCK and BMAL1, transcription factors of the mammalian circadian clock. Quantification of Presenilin‐2 RNA shows that its expression is non‐rhythmic in many peripheral tissues (heart, muscle, kidney, spleen, and thymus). Note, though, that careful analysis of the liver data shows that Presenilin‐2 RNA exists in distinct isoforms in this tissue, and that rhythmicity is restricted to only a subset of these RNA isoforms. These data indicate a unique mode of regulation of Presenilin‐2 transcripts, the circadian control of which appears to happen at the transcriptional and post‐transcriptional levels.

• BMAL1
• Circadian rhythm
• CLOCK
• E‐box
• Presenilin
• Splicing
• Transcription
• Clock genes