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Histone monoubiquitination by Clock-Bmal1 complex marks Per1 and Per2 genes for circadian feedback

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We propose that the effects of cumulative loss of surface receptor with fast-internalizing, slow-recycling, lysosome-targeting agonists, along with increases in -arrestin-induced desensitization, become more apparent with time, eventually overriding any positive effects associated with noncanonical signaling