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 ]
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Life Sciences
23.03.2018 | Materials Sciences
23.03.2018 | Process Engineering