Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

More code cracking

02.08.2012
3 related studies help uncover the rules governing gene transcription

A trio of groundbreaking publications from researchers in Northwestern University's Physical Sciences-Oncology Center (PS-OC) report important methodological advances that will enable a better understanding of how gene expression is regulated, both in normal cells and in cancer cells. This knowledge could lead to the development of more effective therapeutic agents to treat cancer patients.

The three papers, published recently in the journals Nature Genetics, Nature Biotechnology and Nature, focus on nucleosomes, a basic unit of DNA packaging, and may help to uncover the rules governing gene transcription.

The late Jonathan Widom of Northwestern is senior author of the Nature paper that describes a new method for mapping nucleosomes. His longtime collaborator Eran Segal of the Weizmann Institute in Israel is senior author of two papers that build on his and Widom's earlier discovery of a "second DNA code."

"It is becoming increasingly clear that acquired mutations in the machinery that underlies the way in which DNA is packaged into chromatin are major drivers of the development of tumors in humans," said Jonathan Licht, M.D., the Northwestern PS-OC's senior investigator. Chromatin is a complex of DNA and proteins that when compacted forms chromosomes.

"The work of the PS-OC, including these new studies, has allowed the elucidation of the normal rules by which chromatin is arranged in the cell," he said. "This will help us to understand what's going wrong in cancer and how that might be remedied." Licht is the Johanna Dobe Professor and chief of the division of hematology/oncology at Northwestern's Feinberg School of Medicine and an associate director of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Six years ago, Widom and Segal reported in Nature the discovery of a second DNA code that explains the placement of nucleosomes, spool-like structures in which the DNA loops around a protein complex. (The first code is DNA's genetic code, which specifies the composition of cellular proteins.) Nucleosomes control access to the DNA. Widom and Segal found there are certain DNA sequences that favor or disfavor the location of these nucleosomes.

Widom, whose research focused on chromatin packaging and gene regulation, and Segal, a computational biologist, continued their studies on sequence preferences for nucleosome formation as part of a project funded by Northwestern's Physical Sciences-Oncology Center.

Widom directed the center until his untimely death last year and was the William Deering Professor of Molecular Biosciences in the Weinberg College of Arts and Sciences. Segal has been a member of the center since its inception in 2009.

"This new work of Jon Widom's lab, reported in Nature, adds greatly to the ability to measure the locations of nucleosomes with unprecedented accuracy, which is needed to decipher the code in the DNA as reported in our two recent papers," Segal said.

In the papers by the Segal group, one in Nature Genetics and the other in Nature Biotechnology, Segal and his colleagues developed an elegant experimental system that allows them to accurately measure the effects of DNA sequences that disfavor the formation of nucleosomes on transcriptional regulation.

The new technology makes it possible to simultaneously introduce tens of thousands of DNA regions into tens of thousands of living cells -- each region in a separate cell -- in a planned and systematic manner, and to measure the results of each such change with great precision and within a single experiment.

Using this system, the Segal group demonstrated that sequences favoring the formation of nucleosomes do indeed have a significantly negative impact on transcription. Transcription is the copying of specific sequences in the DNA into similar molecules called RNA, which are intermediaries in the flow of information between the DNA and protein production. Both of the Segal papers acknowledge the intellectual contribution of Widom to their work.

The third paper, published in Nature and reporting on work completed in the Widom laboratory after his death, describes another major methodological advance. This novel technique permits the location of nucleosomes in the genome to be mapped with much higher accuracy than was previously possible. Not only will this technique enable a much better understanding of transcriptional regulation, but it should also help scientists to understand other features of DNA biology.

Ji-Ping Wang, who directs the bioinformatics core of the PS-OC, played a major role in the development of this technique.

"This is another example of how Jon's great knowledge in biochemistry and biophysics allowed him to suggest a way to scale up an existing experimental technique into modern tools that would allow genome-wide mapping of nucleosomes," Segal said. "Jon also was closely involved in our work and provided invaluable insights and suggestions into all aspects of the research."

The Northwestern Physical Sciences-Oncology Center focuses on applying physical sciences approaches to understanding the fundamental principles underlying aberrant gene expression in cancer. Funded by the National Cancer Institute, the center is a collaboration of the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Megan Fellman | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

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

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>