A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock.

A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Research Abstract Details 

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A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Abstract Text:

Akira Matsumoto,Maki Ukai-Tadenuma,Rikuhiro G Yamada,Jerry Houl,Kenichiro D Uno,Takeya Kasukawa,Brigitte Dauwalder,Taichi Q Itoh,Kuniaki Takahashi,Ryu Ueda,Paul E Hardin,Teiichi Tanimura,Hiroki R Ueda,Akira Matsumoto,Maki Ukai-Tadenuma,Rikuhiro G Yamada,Jerry Houl,Kenichiro D Uno,Takeya Kasukawa,Brigitte Dauwalder,Taichi Q Itoh,Kuniaki Takahashi,Ryu Ueda,Paul E Hardin,Teiichi Tanimura,Hiroki R Ueda,

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.

A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Publishing Authors By Initials

A Matsumoto,M Ukai-Tadenuma,RG Yamada,J Houl,KD Uno,T Kasukawa,B Dauwalder,TQ Itoh,K Takahashi,R Ueda,PE Hardin,T Tanimura,HR Ueda,A Matsumoto,M Ukai-Tadenuma,RG Yamada,J Houl,KD Uno,T Kasukawa,B Dauwalder,TQ Itoh,K Takahashi,R Ueda,PE Hardin,T Tanimura,HR Ueda,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Genes & development

VOLUME: 21

Page Numbers: 1687-700

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 19

MONTH: 06

YEAR: 2007

A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711660

A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: physiology

Chemical & Substance for Abstract: A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Information

Substance Name: clockwork orange protein, Drosophila

Registry Number: 0

Grant and Affiliation Information for A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock.

AFFILIATION: Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, Kobe, Hyogo, Japan.

Country: United States

AGENCY: United States NINDS

GRANT: NS052854

ACRONYM: NS

MEDLINETA: Genes Dev

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