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Researchers Investigate Gene Linked With Circadian Liver Clock

r2 genes followed the same arc and temporal patterns, suggesting the influence of a shared systemic cue (the authors discovered this was elevated temperature). Since mPer2 transcription can be induced by heat shock and since the mPer2 gene contains binding sites for the transcription factors (HSFs) that activate heat-shock proteins, future experiments will probe whether these transcription factors and binding sites help mediate temperature-dependent mPer2 expression.

By controlling liver clock function with the flip of a molecular switch, the authors showed that only 10% of circadian genes follow temporal expression patterns in the absence of liver oscillators. The authors think these genes probably respond to physical or chemical signals controlled by the master SCN pacemaker. mPer2 is a strong candidate as one of the systemically regulated synchronizers because its expression pattern is almost identical with or without a functional liver clock. A systemically driven mPer2 transcription cycle would provide the necessary link to synchronize the phase of the peripheral oscillator to that of the central system.

Future studies are necessary to illuminate the molecular mechanisms of systemic mPer2 transcription. A number of environmental cues, including elevated temperature and oxidative stress, activate HSF1. It’s possible that HSF1, by sensing rhythmic changes in metabolism, synchronizes peripheral clocks by modulating mPer2 expression. These and similar questions about the signaling pathways that bring all the body’s clocks into the same phase can be explored with the novel transgenic mouse model described here.

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