RESUMO
The current model of the mammalian circadian clock describes cell-autonomous and negative feedback-driven circadian oscillation of Cry and Per transcription as the core circadian rhythm generator. However, the actual contribution of this oscillation to circadian rhythm generation remains undefined. Here we perform targeted disruption of cis elements indispensable for cell-autonomous Cry oscillation. Mice lacking overt cell-autonomous Cry oscillation show robust circadian rhythms in locomotor activity. In addition, tissue-autonomous circadian rhythms are robust in the absence of overt Cry oscillation. Unexpectedly, although the absence of overt Cry oscillation leads to severe attenuation of Per oscillation at the cell-autonomous level, circadian rhythms in Per2 accumulation remain robust. As a mechanism to explain this counterintuitive result, Per2 half-life shows cell-autonomous circadian rhythms independent of Cry and Per oscillation. The cell-autonomous circadian clock may therefore remain partially functional even in the absence of overt Cry and Per oscillation because of circadian oscillation in Per2 degradation.
Assuntos
Relógios Circadianos , Ritmo Circadiano , Animais , Relógios Circadianos/genética , Ritmo Circadiano/genética , Criptocromos/genética , Criptocromos/metabolismo , Locomoção , Mamíferos/metabolismo , Camundongos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismoRESUMO
The cyclization reaction of diarylethenes having an azulene ring occurs only via higher excited states. Novel diarylethenes having an azulene ring with a strong donor or acceptor were synthesized and examined in these reactions. A derivative having an electron-donating 1,3-benzodithiol-2-ylidenemethyl group at the 1-position of the azulene ring showed photochromism, whereas neither a derivative having a π-conjugated electron-donating group at the 3-position of the azulene ring nor derivatives having a π-conjugated electron-withdrawing group at the 1- or 3-position of the azulene ring showed any photochromism. The photoreactivities of these compounds were explained by calculating forces and bond orders on the excited states using density functional theory (DFT) and time-dependent (TD)-DFT.