A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery
A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery
Significance Circadian clocks are endogenous molecular oscillators that drive daily rhythms of physiology and behavior. The mammalian clock, intrinsic to most cells and tissues, is built on a conserved negative feedback loop in which a heterodimeric transcription factor, circadian locomotor output cycles kaput (CLOCK)-brain, muscle Arnt-like 1 (BMAL1), drives the transcription of its specific inhibitor proteins. This study shows that CLOCK-BMAL1 is associated with a clock-driven, rhythmically expressed coactivator protein, TRAP150 (thyroid hormone receptor-associated protein-150), that promotes the binding of CLOCK-BMAL1 to DNA and links it to the basic transcriptional machinery. The activity and oscillation of TRAP150 define a positive feedback loop within the core clock and provide a potential mechanism for the precise timing of circadian transcription cycles.
- Harvard University United States
Feedback, Physiological, Chromatin Immunoprecipitation, Transcription, Genetic, Immunoblotting, ARNTL Transcription Factors, CLOCK Proteins, Mass Spectrometry, Cell Line, Circadian Rhythm, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Animals, Humans, Immunoprecipitation, RNA Interference, Transcription Factors
Feedback, Physiological, Chromatin Immunoprecipitation, Transcription, Genetic, Immunoblotting, ARNTL Transcription Factors, CLOCK Proteins, Mass Spectrometry, Cell Line, Circadian Rhythm, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Animals, Humans, Immunoprecipitation, RNA Interference, Transcription Factors
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