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CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN
CLOCKWORK ORANGE helps activate the CLOCK-CYCLE system through the fruit fly version of CLOCK INTERACTING PROTEIN CIRCADIAN
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Abstract
CWO inhibition of CIPC repression promotes CLK-CYC transcription.
- CWO target genes are upregulated in the absence of CWO repression and are preferentially expressed in brain pacemaker neurons.
- A putative ortholog of mouse Clock Interacting Protein Circadian (Cipc) was identified as a key player in regulating CLK-CYC transcription.
- Reducing or eliminating Drosophila Cipc expression is associated with a shortened circadian period, while overexpression lengthens the period.
- Cipc represses CLK-CYC transcription in vivo variably across different genes, with the strongest repression on per.
- Long period rhythms in cwo mutant flies are largely rescued by reducing Cipc expression, which also restores CLK-CYC transcription levels.
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