Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Molecular partners required for appropriate neuronal gene repression


In their efforts to understand the complex biology of life, scientists often seek to isolate individual elements of the puzzle for study, to break the problem down to a more manageable size. Single genes and molecules are closely analyzed to better understand their specific interactions with other single entities within larger systems.

Sometimes, however, this approach misses important aspects of biology that depend on higher levels of organization. Sometimes putting a few of the pieces back together again reveals new information that would otherwise remain obscured.

A new study by researchers at The Wistar Institute demonstrates this point. Aiming for insights into the intricate biochemistry governing gene regulation, the scientists investigated the activity of a recently discovered enzyme pivotally involved in this process. A report on their findings, which may have long-term implications for treating depression and other psychiatric disorders, was published online by Nature today.

The enzyme’s function is to remove methyl groups from histones to modify them in ways that trigger gene repression. Eight histones comprise a nucleosome, and long strings of nucleosomes coil in turn into chromatin, the basic material of chromosomes. In the body’s scheme for safely storing genes away until needed, DNA is tightly looped around the histones, kept secure by enzymes similar to the one studied by the Wistar team until made accessible by the activity of related enzymes responsible for gene expression.

What the scientists found was that while the enzyme was able to demethylate its target histone when the pair was in isolation, it was unable to do so when the histone was placed in the more complex and realistic setting of a nucleosome. They then coupled the enzyme with other molecules with which it is known to complex to discover that one of them enabled the enzyme to act upon the histone and is, in fact, required for the enzyme’s effectiveness in vivo.

"The real field of action for these enzymes is chromatin, not the histones," says Ramin Shiekhattar, Ph.D., an associate professor at Wistar and senior author on the Nature study. "In our experiments, the enzyme alone was active with histones, but when we tested it on chromatin, we saw something very interesting – the enzyme was completely inactive on nucleosomes. On the other hand, the complex containing the enzyme worked well. The goal then became to determine what in the complex conferred this capability on the enzyme."

The complex, known as BHC, contains five components, including the enzyme studied by Shiekhattar and his coworkers, referred to either as BHC110 or LSD1. Further experiments by the team revealed that the enzyme requires the presence of another member of the complex called CoREST to act on nucleosomes.

Intriguingly, the enzyme in question, which helps to appropriately repress neuronal genes in non-neuronal cells and tissues, fits into the same extended enzyme family that includes monoamine oxidases, psychoactive enzymes that oxidize dopamine and norepinephrin. Inhibitors of these enzymes have long been used to treat depression, certain other psychiatric and emotional disorders, and Parkinson’s disease. A clearer understanding of this particular gene-repression system might suggest new approaches to treatments for an array of psychiatric conditions.

The lead author on the Nature study is Min Gyu Lee. Christopher Wynder and Neil Cooch are coauthors. Senior author Shiekhattar is an associate professor in two programs at Wistar, the gene expression and regulation program and molecular and cellular oncogenesis program. Support for the research was provided by the National Institutes of Health.

Franklin Hoke | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

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...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

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...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

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...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>