The circadian regulation of Presenilin-2 gene expression.
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.
Bélanger
Valérie
V
Douglas Hospital Research Centre, McGill University, Montreal, Quebec, Canada.
Picard
Nathalie
N
Cermakian
Nicolas
N
D056930:ARNTL Transcription Factors; D017398:Alternative Splicing; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D056926:CLOCK Proteins; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D016133:Polymerase Chain Reaction; D053766:Presenilin-2 / Q000096:biosynthesis* / Q000502:physiology*; D020033:Protein Isoforms; D012323:RNA Processing, Post-Transcriptional; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D053766:Presenilin-2; D020033:Protein Isoforms; D015534:Trans-Activators; C538961:Bmal1 protein, mouse; C538944:Clock protein, mouse