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

Jan 15, 2010Genes to cells : devoted to molecular & cellular mechanisms

The protein TIEG1 controls the Bmal1 gene to regulate the body’s internal clock

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Diurnal variation of Tieg1 mRNA and nuclear TIEG1 protein levels was observed in the mouse liver, with peaks at day/night transition and midnight.

The circadian clock regulates daily rhythms in various physiological processes and is influenced by external cues such as light and feeding.
TIEG1, a transcriptional repressor, was found to bind to the Bmal1 gene promoter, inhibiting its transcriptional activity.
The repression of Bmal1 by TIEG1 is additive to the repression exerted by REV-ERBalpha, another known repressor.
Knock-down of TIEG1 using siRNA resulted in a shortening of cellular bioluminescence rhythms associated with Bmal1 and Per2.
These observations suggest TIEG1 plays a significant role in regulating the normal oscillation of the circadian clock.

AI simplified

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-ERBalpha, 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.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief