Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Urgent! How genes tell cellular construction crews, 'Read me now!'

14.08.2013
Stowers researchers show that DNA sequences at the beginning of genes -- at least in fruit flies -- contain more information than previously thought

When egg and sperm combine, the new embryo bustles with activity. Its cells multiply so rapidly they largely ignore their DNA, other than to copy it and to read just a few essential genes. The embryonic cells mainly rely on molecular instructions placed in the egg by its mother in the form of RNA.


The dorsal-ventral patterning gene snail (shown in red) is one of the few genes that are active before as well as after the midblastula transition. The segmentation gene paired (shown in green) is turned on during the transition. Cell nuclei are shown in blue.

Credit: Image: Courtesy of Kai Chen

The cells translate these RNA molecules into proteins that manage almost everything in the first minutes or hours of the embryo's life. Then, during the so-called midblastula transition, cells start transcribing massive amounts of their own DNA. How embryonic cells prepare for this moment, and how they flag a small set of genes for transcription before that, holds important information about normal development and disease in animals and in humans.

A new study that sheds light on these questions appears in the Aug. 13 issue of eLife Sciences, authored by researchers at the Stowers Institute for Medical Research. The team, led by Associate Investigator Julia Zeitlinger, Ph.D., shows that in the fruit fly Drosophila melanogaster, genes active in the first two hours of a fertilized egg are read quickly due to special instructions at the beginning of each gene, in a region aptly named the "promoter."

Within each promoter region, different combinations of short control elements or "boxes" form a code that instructs specialized construction crews, called RNA polymerases, where and when to start transcribing. Researchers long thought that once an RNA polymerase appears at the worksite it would quickly finish the job.

"The most important result is that promoters are different," Zeitlinger says. "The general paradigm for a long time has been a promoter is a promoter. But really what we see is that they have different functions."

As a postdoctoral fellow at MIT, Zeitlinger unexpectedly discovered that sometimes RNA polymerase II pauses at the beginning of a gene as if taking a lunch break. More often than not, pausing occurred at genes important for development. Zeitlinger thought pausing may help get these molecular construction workers on site before a huge work order is due.

"We were wondering whether pausing was being used for preparing global gene activation during the midblastula transition," says Kai Chen, PhD, a former graduate student in Zeitlinger's lab and the study's first author. "We expected to see widespread pausing before that transition."

The fruit fly Drosophila melanogaster was a perfect test subject. This fly embryo takes two hours to reach the midblastula transition providing plenty of time to analyze what happens during this early period. Furthermore, decades of previous research on the flies provided context to guide the work.

Chen used a method called ChIP-seq, which can locate RNA polymerase II molecules on any gene. Paused polymerases would show up only at the beginning of genes. Working polymerases, on the other hand, would be found throughout the gene body.

The results took the Stowers team by surprise. Before the midblastula transition, RNA Polymerase II appeared to rarely pause as it transcribed roughly 100 early genes. And no construction crews were sitting idle on inactive genes in preparation for the midblastula transition. Pausing only became widespread only during the midblastula transition itself.

"What we found was not what we expected at all," Zeitlinger says. Before the midblastula transition, instead of preparing for a huge workload the construction crews were busy completing rush jobs. "The polymerase has to come to the promoter and immediately transcribe because there's so little time to do the job. That's one way of making transcription faster. "

When Chen and colleagues computationally compared the DNA sequences of promoters where pausing occurred with those where it didn't, a pattern emerged. They found that three different types of promoters correlated with the construction crew's pausing behavior.

The genes that RNA Polymerase II reads before the midblastula transition were often preceded by a promoter that seemed to yell, "Urgent! Don't even think about pausing." These promoters contain what's known as a TATA-box, named for its conserved arrangement of nucleotides, most commonly TATAA.

As cell division slows down during the midblastula transition, cells have the luxury of pausing, perhaps to fine-tune when transcription begins, Zeitlinger says.

These midblastula genes were regulated by promoters that contain a variety of specific promoter elements associated with paused RNA polymerase, including GAGA, Downstream Promoter Element (DPE), Motif Two Element (MTF) and Pause Button (PB).

The team also found a third type of promoter, which contained both the TATA-box and the pausing sequences. At these genes, RNA polymerase II does not pause initially but begins to pause during the midblastula transition.

Zeitlinger hopes learning more about promoters will give clues to the functions of unknown genes. Because these promoter sequences are not specific to flies, the differences among promoter types may be conserved in other animals as well.

"My lab is interested in understanding how development or even diseases are encoded in the genome," Zeitlinger says. "If we understand transcription, then we can predict a lot of what genomes encode, in terms of disease or differences between individuals."

"Promoters had been seen by some scientists as sort of boring," she adds, "but now, they are starting to get really interesting."

Other contributors include Jeff Johnston, Wanqing Shao, Samuel Meier and Cynthia Staber, all from the Stowers Institute.

The study was funded by the Stowers Institute for Medical Research, the Pew Charitable Trust and an NIH New Innovator Award.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife Virginia opened the Institute in 2000. Since then, the Institute has spent over 900 million dollars in pursuit of its mission.

Currently the Institute is home to nearly 550 researchers and support personnel; over 20 independent research programs; and more than a dozen technology development and core facilities. Learn more about the Institute at http://www.stowers.org.

Gina Kirchweger | EurekAlert!
Further information:
http://www.stowers.org

More articles from Life Sciences:

nachricht Bacteria as pacemaker for the intestine
22.11.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Researchers identify how bacterium survives in oxygen-poor environments
22.11.2017 | Columbia 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: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Corporate coworking as a driver of innovation

22.11.2017 | Business and Finance

PPPL scientists deliver new high-resolution diagnostic to national laser facility

22.11.2017 | Physics and Astronomy

Quantum optics allows us to abandon expensive lasers in spectroscopy

22.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>