Scientists Unwind a Circadian Clock Mystery



Researchers from RIKEN, Hiroshima University and the University of Michigan say a particular gene plays a key role in influencing circadian rhythms. In their study (A Novel Protein, CHRONO, Functions as a Core Component of the Mammalian Circadian Clock), which appears in PLOS Biology, 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 circadian clock genes, regulating their transcription.


The new gene, dubbed Chrono, shows that it functions as a transcriptional repressor of the negative feedback loop in the mammalian clock. The Chrono protein 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.


“In vivo loss-of-function studies of Chrono including Avp neuron-specific knockout (KO) mice display a longer circadian period of locomotor activity. Chrono KO also alters the expression of core clock genes and impairs the response of the circadian clock to stress,” add investigators. “Chrono forms a complex with the glucocorticoid receptor and mediates glucocorticoid response. Our comprehensive study spotlights a previously unrecognized clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock.”


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