Characterisation of the epidermal diurnal transcriptome of mice with K14-Cre-driven Bmal1 knockout
To preserve a state of health, mammals employ an integrated network of molecular oscillators to drive daily rhythms of tissue-specific homeostatic processes. Importantly, the output, structure and coherence of this network is compromised by physiological ageing, disease and lifestyle changes. Yet, the key signalling nodes in this network, their underlying mechanisms of communication, and potential for therapeutic intervention, remain undefined. To dissect this system, we construct a minimal clock network consisting of two communicating nodes: the peripheral epidermal clock and central brain clock. We show that communication between the brain and epidermal clocks is sufficient for wild-type core clock activity and specific homeostatic processes, but inputs from other clock nodes are essential for full daily physiology. Unexpectedly, we find evidence that the epidermal clock selectively suppresses or interprets systemic signals to ensure coherence of specific homeostatic processes, identifying an unrecognised gatekeeper role for peripheral clocks. Together, we introduce a novel approach for dissecting a tissues daily physiology, and in turn identify key signalling nodes required to maintain epidermal homeostasis. Overall design: The diurnal transcriptome of the skin epidermis was profiled for mice in which circadian clock activity was absent in the skin epidermis, but present in all other tissues. Profiling was undertaken by performing RNA-seq of epidermis samples taken at four hour intervals throughout the day (four biological replicates per timepoint). Subsequently, a comparison with gene expression rhythmicity in WT epidermis was performed using the DryR algorithm.