The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator

@article{Preitner2002TheON,
  title={The Orphan Nuclear Receptor REV-ERB$\alpha$ Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator},
  author={Nicolas Preitner and Francesca Damiola and Luis-Lopez-Molina and Joszef Zakany and Denis Duboule and Urs Albrecht and Ueli Schibler},
  journal={Cell},
  year={2002},
  volume={110},
  pages={251-260}
}
Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components… Expand
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References

SHOWING 1-10 OF 107 REFERENCES
Interacting molecular loops in the mammalian circadian clock.
TLDR
Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal 1 loop. Expand
CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP.
TLDR
Evidence is presented that circadian Dbp transcription requires the basic helix-loop-helix-PAS protein CLOCK, an essential component of the negative-feedback circuitry generating circadian oscillations in mammals and fruit flies. Expand
Posttranslational Mechanisms Regulate the Mammalian Circadian Clock
TLDR
Analysis of clock proteins in m CRY-deficient mice shows that the mCRYs are necessary for stabilizing phosphorylated mPER2 and for the nuclear accumulation of mPER1, mper2, and CKIepsilon, and provides in vivo evidence that casein kinase I delta is a second clock relevant kinase. Expand
Invited review: regulation of mammalian circadian clock genes.
  • U. Albrecht
  • Biology, Medicine
  • Journal of applied physiology
  • 2002
TLDR
This mini-review will summarize the advances that have led to a new understanding of the molecular basis of the circadian clock in mammals at the molecular level. Expand
Resetting central and peripheral circadian oscillators in transgenic rats.
TLDR
It is hypothesize that a self-sustained circadian pacemaker in the SCN entrains circadian oscillators in the periphery to maintain adaptive phase control, which is temporarily lost following large, abrupt shifts in the environmental light cycle. Expand
Circadian Transcription
TLDR
This study compared the E-Box-containing minimal promoters of vasopressin andcyclin B1, two genes that can respond to the transcriptional oscillators driving the circadian clock and cell cycle, respectively, to help elucidate the manner in which discreet DNA modules associate to either augment or restrain the activation of potential circadian E- boxes in response to competing regulatory signals. Expand
The mPer2 gene encodes a functional component of the mammalian circadian clock
TLDR
Evidence that an mPer gene functions in the circadian clock is provided, and mPer2 is defined as a component of the mammalian circadian oscillator. Expand
Interactivating feedback loops within the mammalian clock: BMAL1 is negatively autoregulated and upregulated by CRY1, CRY2, and PER2.
TLDR
The transcriptional potency of CRY is predominant within the mammalian clock, suggesting a clearance mechanism for CRY in period maintenance, and it is proposed that a BMAL1 negative feedback loop interlocks with the CRY and PER2negative feedback loop by inter-activation, forming a third positive forward loop. Expand
Targeted Disruption of the mPer3 Gene: Subtle Effects on Circadian Clock Function
TLDR
It is shown that mouse PER3 is not necessary for circadian rhythms in mice, and the level of expression of the mutant transcript was lower than that in wild-type controls. Expand
Interlocked feedback loops within the Drosophila circadian oscillator.
TLDR
The results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback loops: a per-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk loop,Which is repression by dClK- CYC and derepressed by PerIOD-tIM. Expand
...
1
2
3
4
5
...