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• W1997932809 abstract "Mammalian circadian rhythms are generated by a negative feedback loop in which PERIOD (PER) proteins accumulate, form a large nuclear complex (PER complex), and bind the transcription factor CLOCK-BMAL1, repressing their own expression. We found that mouse PER complexes include the Mi-2/nucleosome remodelling and deacetylase (NuRD) transcriptional corepressor. Unexpectedly, two NuRD subunits, CHD4 and MTA2, constitutively associate with CLOCK-BMAL1, with CHD4 functioning to promote CLOCK-BMAL1 transcriptional activity. At the onset of negative feedback, the PER complex delivers the remaining complementary NuRD subunits to DNA-bound CLOCK-BMAL1, thereby reconstituting a NuRD corepressor that is important for circadian transcriptional feedback and clock function. The PER complex thus acquires full repressor activity only upon successful targeting of CLOCK-BMAL1. Our results show how specificity is generated in the clock despite its dependence on generic transcriptional regulators and reveal the existence of active communication between the positive and negative limbs of the circadian feedback loop." @default.
• W1997932809 created "2016-06-24" @default.
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• W1997932809 date "2014-12-01" @default.
• W1997932809 modified "2023-09-30" @default.
• W1997932809 title "Specificity in Circadian Clock Feedback from Targeted Reconstitution of the NuRD Corepressor" @default.
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• W1997932809 doi "https://doi.org/10.1016/j.molcel.2014.10.017" @default.
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