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| Status |
Public on Jul 23, 2021 |
| Title |
CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the Drosophila ortholog of CLOCK INTERACING PROTEIN, CIRCADIAN (RNA-Seq) |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The Drosophila circadian clock is driven by a transcriptional feedback loop in which the bHLH transcription factor CLOCK-CYCLE (CLK-CYC) binds E-boxes to transcribe genes encoding the PERIOD-TIMELESS (PER-TIM) repressor, which releases CLK-CYC from E-boxes to inhibit transcription. The bHLH-Orange transcription factor CLOCKWORK ORANGE (CWO) reinforces repression by binding E-boxes to displace CLK-CYC, but also acts through an unknown mechanism to promote CLK-CYC transcription. To determine how CWO activates CLK-CYC transcription, we identified CWO DNA binding targets that are upregulated in the absence of CWO repression, conserved in mammals and preferentially expressed in brain pacemaker neurons. Among the genes identified was the Drosophila ortholog of mammalian Clock Interacting Protein Circadian (Cipc) that acts to repress CLOCK-BMAL1 transcription. Reducing or eliminating Drosophila Cipc expression shortens circadian period while overexpressing Cipc lengthens circadian period in flies, consistent with previous analysis showing that Drosophila Cipc represses CLK-CYC transcription in S2 cell culture. Long period rhythms of cwo mutant flies are largely rescued when Cipc expression is reduced or eliminated, indicating that increased Cipc expression mediates period lengthening of cwo mutants. These results suggest a mechanism for CWO-dependent CLK-CYC activation: CWO inhibition of CIPC repression promotes CLK-CYC transcription. Such a mechanism may be conserved given that orthologs of cwo and Cipc carry out analogous roles in the mammalian circadian clock.
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| Overall design |
RNA-seq: mRNA profiles of heads from Drosophila wild type (WT) and cwo5073 mutant at six different timepoints, ZT 02, ZT 06, ZT 10, ZT 14, ZT 18, ZT 22
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| Contributor(s) |
Rivas GS, Zhou J, Merlin C, Hardin PE |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Jan 18, 2021 |
| Last update date |
Jul 26, 2021 |
| Contact name |
Paul Hardin |
| E-mail(s) |
[email protected]
|
| Phone |
4075419203
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| Organization name |
Texas A&M University
|
| Street address |
3258 TAMU Dept of Biology Buttler Hall room 100H
|
| City |
College Station |
| State/province |
Texas |
| ZIP/Postal code |
77843 |
| Country |
USA |
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| Platforms (1) |
| GPL19132 |
Illumina NextSeq 500 (Drosophila melanogaster) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE165044 |
CLOCKWORK ORANGE promotes CLOCK-CYCLE activation via the putative Drosophila ortholog of CLOCK INTERACTING PROTEIN CIRCADIAN |
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| Relations |
| BioProject |
PRJNA693024 |
| SRA |
SRP302239 |
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