The circadian demethylation of a unique intronic deoxymethylCpG-rich island boosts the transcription of its cognate circadian clock output gene.
Fiche publication
Date publication
février 2023
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre
Tous les auteurs :
Misra N, Damara M, Ye T, Chambon P
Lien Pubmed
Résumé
We demonstrate that there is a tight functional relationship between two highly evolutionary conserved cell processes, i.e., the circadian clock (CC) and the circadian DNA demethylation-methylation of cognate deoxyCpG-rich islands. We have discovered that every circadian clock-controlled output gene (CCG), but not the core clock nor its immediate-output genes, contains a single cognate intronic deoxyCpG-rich island, the demethylation-methylation of which is controlled by the CC. During the transcriptional activation period, these intronic islands are demethylated and, upon dimerization of two YY1 protein binding sites located upstream to the transcriptional enhancer and downstream from the deoxyCpG-rich island, store activating components initially assembled on a cognate active enhancer (a RORE, a D-box or an E-box), in keeping with the generation of a transcriptionally active condensate that boosts the initiation of transcription of their cognate pre-mRNAs. We report how these single intronic deoxyCpG-rich islands are instrumental in such a circadian activation/repression transcriptional process.
Mots clés
YY1 protein, circadian DNA demethylation-methylation, circadian clock (CC), circadian transcription, intronic deoxyCpG islands
Référence
Proc Natl Acad Sci U S A. 2023 02 21;120(8):e2214062120