Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key factor combines day and night to hold back morning

18.02.2011
As in manmade timepieces, the movements of the genetic clockworks that lie behind circadian cycles involve a remarkable amount of complexity. Researcher's from RIKEN's Laboratory for Systems Biology report how delayed feedback repression is a key factor in mammalian clock function.

The mammalian circadian clock is thought to arise from the interactions of around 20 transcription factors with specific DNA sequences associated with morning, day, and night expression. Existing models of this genetic network can readily explain the basis for the day and night activities, but the mechanism underlying morning expression remains incompletely understood.

It is thought that delayed negative feedback exerted by the morning (E/E? box) inhibitor Cryptochrome 1 (Cry1), which is itself expressed in evening, plays an important role in keeping the biological clock on time. But just how it achieves this effect is unknown.

Maki Ukai-Tadenuma and Rikuhiro G. Yamada of the Laboratory for Systems Biology (Hiroki R. Ueda, Project Leader), along with colleagues in the Universities of Memphis (USA) and Fribourg (Switzerland), now report how delayed feedback repression is a key factor in mammalian clock function. Published in Cell, this work shows the role of Cry1 as mediator of delayed negative feedback repression and fleshes out the current understanding of the circadian circuitry.

The team began by looking into the basis for the evening expression of Cry1 using reporter genes coding for the luciferase protein to detect transcriptional activity, and found that the Cry1 promoter region induces the expression of genes carrying the daytime expression motif. A closer look at Cry1’s DNA revealed that its intronic region contains a separate sequence that induces nighttime clock genes. They next stitched together a construct including these promoter and intron regions, and ran another reporter assay to observe its behavior, and found that its expression switched on in circadian evening, suggesting that this in-between expression time is a result of the combination of day and night regulatory elements. To test this model, the team tried to rescue clock function in cells with homozygous deletions of both Cry1 and Cry2 by inducing the evening expression of exogenous Cry1. They found that while the Cry1 promoter region alone was ineffective, when the promoter and intron regions were used in conjunction, the gene’s circadian rhythmicity was restored.

Using this same set-up, Ukai-Tadenuma and Yamada next tried changing the onset time of Cry1 expression, and found that as expression neared midday, meaning that the normal phase delay was reduced, the amplitude of circadian oscillations grew smaller, in line with predictions. Similarly, prolonging the delay of exogenous Cry1 expression caused an increase in the length of the restored cycle.

The team's findings were recapitulated by a relatively simple phase vector model, which not only successfully reproduces the findings from the current study, but numerous other aspects of the circadian clock network as well.

"In 1990, Paul Hardin at Texas A&M pointed out the importance of delayed feedback repression in biological clocks, but it has taken 21 years to work out the mechanism behind it," says Ueda. "We will continue exploring whether the current minimal transcriptional network model is complete, or whether new regulatory systems remain to be discovered."

[ Contact ]
Douglas Sipp : sipp(at)cdb.riken.jp
TEL : +81-78-306-3043
RIKEN CDB, Office for Science Communications and International Affairs

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht New gene catalog of ocean microbiome reveals surprises
18.08.2017 | University of Hawaii at Manoa

nachricht Organ Crosstalk: Fatty Liver Can Cause Damage to Other Organs
18.08.2017 | Deutsches Zentrum für Diabetesforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New gene catalog of ocean microbiome reveals surprises

18.08.2017 | Life Sciences

Astrophysicists explain the mysterious behavior of cosmic rays

18.08.2017 | Physics and Astronomy

AI implications: Engineer's model lays groundwork for machine-learning device

18.08.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>