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

Tsuyoshi Hirota, Naohiro Kon, Takashi Itagaki, Naosuke Hoshina, Toshiyuki Okano, Yoshitaka Fukada*

*この研究の対応する著者

研究成果: Article査読

23 被引用数 (Scopus)

抄録

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-ERBα, 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.

本文言語English
ページ(範囲)111-121
ページ数11
ジャーナルGenes to Cells
15
2
DOI
出版ステータスPublished - 2010 2

ASJC Scopus subject areas

  • 遺伝学
  • 細胞生物学

フィンガープリント

「Transcriptional repressor TIEG1 regulates Bmal1 gene through GC box and controls circadian clockwork」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル