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This animation depicts a schematic of the murine circadian clock mechanism in a single, pacemaking neuron in the suprachiasmatic nucleus (SCN) of the hypothalamus, where the master pacemaker is located. Circadian clocks allow organisms to display behaviors and processes with a 24-hour rhythm even in the absence of light input. The basic molecular mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a positive transcription factor gene, Bmal1 (also called Mop3). The second loop--the "negative loop"--controls the transcription of genes in the Period and Cryptochrome families, which encode repressor proteins. The loops are intertwined because the proteins PERIOD and CRYPTOCHROME directly repress transcription mediated by the transcription factors CLOCK and BMAL1, whereas the CLOCK:BMAL1 heterodimer drives transcription of the Period and Cryptochrome genes, as well as that of Rev-erb-alpha, which represses Bmal1 expression. Other proteins, such as casein kinase I ε (CKIε) play essential modulatory roles in mammalian circadian timekeeping.
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