Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component

Jun 21, 2007Genes & development

Clockwork Orange is a gene that blocks other genes and helps control the daily biological clock in fruit flies

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

The gene clockwork orange (cwo) is identified as a new core component of the circadian clock in Drosophila.

CWO encodes a transcriptional repressor that works with other proteins to inhibit the activation of certain target genes by the CLK-CYC complex.
In cwo mutant flies, the profiles of target gene mRNAs show high trough values and low oscillation amplitudes.
Behavioral rhythmicity in cwo mutant flies does not persist in constant darkness, indicating a potential link between transcriptional oscillation amplitude and rhythmicity.
These mutant flies exhibit a long period, suggesting delayed repression of target genes.
CWO appears to function primarily in the late night to help regulate the transcription of direct target genes, including its own gene.

AI simplified

Many organisms use circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila, the master clock gene Clock promotes the transcription of several key target genes. Two of these gene products, PER and TIM, repress CLK-CYC-mediated transcription. To recognize additional direct CLK target genes, we designed a genome-wide approach and identified clockwork orange (cwo) as a new core clock component. cwo encodes a transcriptional repressor that synergizes with PER and inhibits CLK-mediated activation. Consistent with this function, the mRNA profiles of CLK direct target genes in cwo mutant flies manifest high trough values and low amplitude oscillations. Because behavioral rhythmicity fails to persist in constant darkness (DD) with little or no effect on average mRNA levels in flies lacking cwo, transcriptional oscillation amplitude appears to be linked to rhythmicity. Moreover, the mutant flies are long period, consistent with the late repression indicated by the RNA profiles. These findings suggest that CWO acts preferentially in the late night to help terminate CLK-CYC-mediated transcription of direct target genes including cwo itself. The presence of mammalian homologs with circadian expression features (Dec1 and Dec2) suggests that a similar feedback mechanism exists in mammalian clocks.

Full Text

Full text is available at the source.

View full text ↗

Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief