Circadian Controlled Transcription in Brain and Peripheral Organs of Juvenile and Adult Mice

Circadian clocks generate daily rhythms of gene expression that influence physiology, disease, and responses to therapeutics, yet how circadian transcription differs between juvenile and adult organisms remains unresolved. Here, we used genome-wide eXcision Repair sequencing (XR-seq) to quantify transcription-coupled repair as an indirect, high-sensitivity measure of transcription. We profiled the brain, liver, kidney, and testis from juvenile and adult C57BL6/J mice across a 24 h cycle and show that XR-seq enables sensitive circadian transcription mapping. In all organs except the testis, rhythmic transcription phases clustered near dawn and dusk. While core clock gene rhythms are largely preserved between juveniles and adults, rhythms of many clock-controlled genes differ markedly by age. Rhythmic genes are strongly organ-specific yet their overlap between ages is limited, indicating substantial developmental changes in circadian control. Together, these data provide a multi-organ map of juvenile versus adult circadian transcription and indicate that adult therapeutic schedules may not translate to juveniles.