Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study suggests new view of gene activation as a dynamic process

11.11.2003


With the sequence of the human genome largely in hand and the majority of genes now available for study, scientists have increasingly turned their attention to better understanding the process of gene regulation. How is a gene turned on? How is a gene turned off? Estimates are that only one in ten genes is active in a given cell at a given time, so these questions are biologically significant. And in many ways, health turns on the appropriate and reliable control of genes. An array of disease conditions can arise if normal gene regulation is perturbed for any reason.



In the case of gene activation, past studies have revealed that specific molecular additions to DNA-packaging proteins called histones are critical to the process. A number of histones are generally involved in the packaging of a single gene, and the picture had emerged of different enzymes adding different molecular groups to different histones to achieve a series of small changes with the collective outcome of turning the gene on. In essence, additions to histones were accumulated until the "on" state was reached.

Now, a new study by researchers at The Wistar Institute reveals the gene-activation process through these molecular modifications to be more dynamic than had been appreciated previously. Specifically, the team’s experiments show that, within the process of turning a gene on, the addition of a molecule called ubiquitin is required and, at a different stage of activation, the removal of ubiquitin is also necessary. A sequence of modifications is therefore involved – including some that may be reversible, it is now clear. The picture of certain molecular groups being added to histones until the cumulative changes result in gene activation now appears inadequate to explain the process. Instead, a new view that places greater emphasis on the specific order of molecular events within the process of gene activation targeting the histones now seems more informative.


A report on the study appears in the November issue of Genes & Development.

"These findings go against the paradigms that scientists have developed for gene activation," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor in the Gene Expression and Regulation Program at The Wistar Institute and senior author on the study. "What’s new and different here is the idea that there is some sort of dynamic process, a required sequence of changes to the histones packaging the DNA, involved in turning genes on. Order is vital. Gene activation is an intricate, highly orchestrated, and highly regulated series of events – as it should be for something so important to life."

The new study underscores emerging ideas that these chemical modifications to histones play an active role in controlling genes. And they do not simply alter the DNA structure to permit activation, as some scientists have thought. Instead, the addition and removal of the ubiquitin group, in this case, actively recruits crucial molecules into the gene-activation process and then releases them at specific times and locations within the gene.

"The histones and the intricate pattern and sequence of modifications that plays upon them are fundamental to this process," Berger says. "Gene activation doesn’t rely only on the enzymes involved in carrying out the process of ’reading’ the gene. Instead, it’s regulated by the underlying DNA template, provided by the associated histones, which helps orchestrate the sequence of events that results in appropriate gene expression. Furthermore, we now know that human disease – cancers and developmental disorders, for example – can result from loss of these histone controls."

The lead author on the Genes & Development study is Karl W. Henry, Ph.D., at The Wistar Institute. Co-authors at Wistar are Anastasia Wyce, Laura J. Duggan, Ph.D., and N.C. Tolga Emre, M.S. The remaining co-authors are Wan-Sheng Lo and Lorraine Pillus at the University of California, San Diego; Cheng-Fu Kao and Mary Ann Osley at the University of Mexico Health Sciences Center; and Ali Shilatifard at the Saint Louis University School of Medicine.


The research was supported by grants from the National Institutes of Health and the National Science Foundation.

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center – one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.upenn.edu/

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>