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 mouse organs remains unresolved. Here, we used genome-wide eXcision Repair sequencing (XR-seq) after cisplatin treatment to quantify transcription-coupled repair on the transcribed strand (TS) as an indirect, high-sensitivity measure of transcription. We profiled the brain, liver, kidney, and testis from juvenile and adult mice across a 24-h cycle and show that XR-seq is enabling sensitive circadian transcription mapping. In all organs of juvenile and adult mice, rhythmic transcription phases clustered near dawn and dusk, but juveniles showed modest, tissue-specific phase shifts. While core clock gene rhythms are largely preserved between juveniles and adults, with only modest, tissue-specific changes in phase and amplitude, clock-controlled rhythms differ markedly by age. Rhythmic genes are strongly organ-specific and overlap between ages across tissues is limited, indicating substantial developmental changes in circadian output. We report age- and tissue-specific circadian regulation of pathways such as signaling, transport, apoptosis, and metabolism. 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.