| RRC ID |
11143
|
| 著者 |
Matsumoto A, Ukai-Tadenuma M, Yamada RG, Houl J, Uno KD, Kasukawa T, Dauwalder B, Itoh TQ, Takahashi K, Ueda R, Hardin PE, Tanimura T, Ueda HR.
|
| タイトル |
A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock.
|
| ジャーナル |
Genes Dev
|
| Abstract |
The Drosophila circadian clock consists of integrated autoregulatory feedback loops, making the clock difficult to elucidate without comprehensively identifying the network components in vivo. Previous studies have adopted genome-wide screening for clock-controlled genes using high-density oligonucleotide arrays that identified hundreds of clock-controlled genes. In an attempt to identify the core clock genes among these candidates, we applied genome-wide functional screening using an RNA interference (RNAi) system in vivo. Here we report the identification of novel clock gene candidates including clockwork orange (cwo), a transcriptional repressor belonging to the basic helix-loop-helix ORANGE family. cwo is rhythmically expressed and directly regulated by CLK-CYC through canonical E-box sequences. A genome-wide search for its target genes using the Drosophila genome tiling array revealed that cwo forms its own negative feedback loop and directly suppresses the expression of other clock genes through the E-box sequence. Furthermore, this negative transcriptional feedback loop contributes to sustaining a high-amplitude circadian oscillation in vivo. Based on these results, we propose that the competition between cyclic CLK-CYC activity and the adjustable threshold imposed by CWO keeps E-box-mediated transcription within the controllable range of its activity, thereby rendering a Drosophila circadian clock capable of generating high-amplitude oscillation.
|
| 巻・号 |
21(13)
|
| ページ |
1687-700
|
| 公開日 |
2007-7-1
|
| DOI |
10.1101/gad.1552207
|
| PII |
gad.1552207
|
| PMID |
17578908
|
| PMC |
PMC1899476
|
| MeSH |
Amino Acid Sequence
Animals
Animals, Genetically Modified
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism
Biological Clocks / genetics*
CLOCK Proteins
Cells, Cultured
Circadian Rhythm / genetics*
Drosophila Proteins / genetics
Drosophila Proteins / physiology*
Drosophila melanogaster / genetics
Drosophila melanogaster / physiology*
E-Box Elements
Gene Expression Regulation
Genome, Insect
Genomics*
Models, Biological
Molecular Sequence Data
Neurons / metabolism
Repressor Proteins / genetics
Repressor Proteins / physiology*
Sequence Homology, Amino Acid
Transcription Factors / physiology
Transcription, Genetic*
|
| IF |
9.527
|
| 引用数 |
119
|
|
WOS 分野
|
GENETICS & HEREDITY
DEVELOPMENTAL BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ショウジョウバエ |
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