Circadian rhythm orthologs drive pulses of heterochronic miRNA transcription in C. elegans
Résumé
Abstract The C. elegans transcriptome exhibits reproducible, periodic patterns that are phase-locked with features of the larval molting cycle, but the gene regulatory networks underlying this interdependency are unknown. We show here that repeated transcriptional pulses of the lin-4 temporal patterning miRNA are generated by cooperative binding between the C. elegans orthologs of master circadian regulators Rev-Erb and ROR to elements upstream of the lin-4 gene. Remarkably, the precise timing and length of lin-4 transcriptional pulses are dictated by the phased overlap of NHR-85 Rev-Erb and NHR-23 ROR temporal expression patterns. We also demonstrate that LIN-42 Period functions in a similar capacity to its circadian orthologs to negatively regulate periodic transcription but does so by limiting the duration of NHR-85 Rev-Erb /NHR-23 ROR cooperative activity at the lin-4 gene. Summary Orthologs of circadian clock genes generate repeated transcriptional pulses of developmental timing genes in C. elegans
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