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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>