論文

査読有り
2010年2月

Transcriptional repressor TIEG1 regulates Bmal1 gene through GC box and controls circadian clockwork

GENES TO CELLS
  • Tsuyoshi Hirota
  • ,
  • Naohiro Kon
  • ,
  • Takashi Itagaki
  • ,
  • Naosuke Hoshina
  • ,
  • Toshiyuki Okano
  • ,
  • Yoshitaka Fukada

15
2
開始ページ
111
終了ページ
121
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/j.1365-2443.2009.01371.x
出版者・発行元
WILEY-BLACKWELL PUBLISHING, INC

The circadian clock controls daily rhythms in many physiologic processes, and the clock oscillation is regulated by external time cues such as light, temperature, and feeding. In mammals, the transcriptional regulation of clock genes underlies the clock oscillatory mechanism, which is operative even in cultured fibroblasts. We previously demonstrated that glucose treatment of rat-1 fibroblasts evokes circadian expression of clock genes with a rapid induction of Tieg1 transcript encoding a transcriptional repressor. Here, we found diurnal variation of both Tieg1 mRNA and nuclear TIEG1 protein levels in the mouse liver with their peaks at day/night transition and midnight, respectively. In vitro experiments showed that TIEG1 bound to Bmal1 gene promoter and repressed its transcriptional activity through two juxtaposed GC boxes near the transcription initiation site. The GC box/TIEG1-mediated repression of Bmal1 promoter was additive to RORE-dependent repression by REV-ERB alpha, a well-known repressor of Bmal1 gene. In cell-based real-time assay, siRNA-mediated knock-down of TIEG1 caused period shortening of cellular bioluminescence rhythms driven by Bmal1-luciferase and Per2-luciferase reporters. These findings highlight an active role of TIEG1 in the normal clock oscillation and GC box-mediated regulation of Bmal1 transcription.

リンク情報
DOI
https://doi.org/10.1111/j.1365-2443.2009.01371.x
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000274177800003&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/j.1365-2443.2009.01371.x
  • ISSN : 1356-9597
  • Web of Science ID : WOS:000274177800003

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