The circadian clock, the tightly regulated internal clock of daily cycle of all living organisms, is controlled by a complex network of genes and proteins.

In the study, the team performed a genome-wide chromatin immunoprecipitation analysis for genes that were the target of BMAL1, a core clock component that binds to many other clock genes, regulating their transcription.
The authors characterize a new circadian gene that they name Chrono. They show that CHRONO functions as a transcriptional repressor of the negative feedback loop in the mammalian clock: the protein CHRONO binds to the regulatory region of clock genes, with its repressor function oscillating in a circadian manner. The expression of core clock genes is altered in mice lacking the Chrono gene, and the mice have longer circadian cycles.
"These results suggest that Chrono functions as a core clock repressor," conclude the authors.
In addition, they demonstrate that the repression mechanism of Chrono is under epigenetic control and links, via a glucocorticoid receptor, to metabolic pathways triggered by behavioral stress.
These findings are confirmed by another study by the University of Pennsylvania, also published in PLOS Biology today. In the study, John Hogenesch and his team prove the existence of Chrono using a computer-based analysis.
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