A transcription factor response element for gene expression during circadian night

Hiroki R. Ueda (), Wenbin Chen, Akihito Adachi, Hisanori Wakamatsu, Satoko Hayashi, Tomohiro Takasugi, Mamoru Nagano, Ken-ichi Nakahama, Yutaka Suzuki, Sumio Sugano, Masamitsu Iino, Yasufumi Shigeyoshi () and Seiichi Hashimoto
Additional contact information
Hiroki R. Ueda: Yamanouchi Pharmaceutical Company, Ltd
Wenbin Chen: Yamanouchi Pharmaceutical Company, Ltd
Akihito Adachi: Kinki University School of Medicine
Hisanori Wakamatsu: Yamanouchi Pharmaceutical Company, Ltd
Satoko Hayashi: Yamanouchi Pharmaceutical Company, Ltd
Tomohiro Takasugi: Yamanouchi Pharmaceutical Company, Ltd
Mamoru Nagano: Kinki University School of Medicine
Ken-ichi Nakahama: Kinki University School of Medicine
Yutaka Suzuki: The University of Tokyo
Sumio Sugano: The University of Tokyo
Masamitsu Iino: The University of Tokyo
Yasufumi Shigeyoshi: Kinki University School of Medicine
Seiichi Hashimoto: Yamanouchi Pharmaceutical Company, Ltd

Nature, 2002, vol. 418, issue 6897, 534-539

Abstract: Abstract Mammalian circadian clocks consist of complex integrated feedback loops1,2,3,4,5,6,7,8,9,10 that cannot be elucidated without comprehensive measurement of system dynamics and determination of network structures11. To dissect such a complicated system, we took a systems-biological approach based on genomic, molecular and cell biological techniques. We profiled suprachiasmatic nuclei and liver genome-wide expression patterns under light/dark cycles and constant darkness. We determined transcription start sites of human orthologues for newly identified cycling genes and then performed bioinformatical searches for relationships between time-of-day specific expression and transcription factor response elements around transcription start sites. Here we demonstrate the role of the Rev-ErbA/ROR response element in gene expression during circadian night, which is in phase with Bmal1 and in antiphase to Per2 oscillations. This role was verified using an in vitro validation system, in which cultured fibroblasts transiently transfected with clock-controlled reporter vectors exhibited robust circadian bioluminescence12.

Date: 2002
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DOI: 10.1038/nature00906

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