Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

It takes two (or more) to tango: how a web of chromosome interaction can help to explain gene regulation in humans

26.04.2006
Gene regulation is a major issue in biology - how are different genes activated in different tissues or at different times in life, and how and which genes interact with each other? A major breakthrough in the understanding of this issue is about to be published in the scientific journal "PLoS Biology" by Miguel R. Branco and Ana Pombo, two Portuguese scientists at the MRC Clinical Sciences Centre, Imperial College London, UK.

The two scientists show that chromosomes in the nucleus of metabolically active cells are largely intermingled, and that this physical contact is associated with their gene activity. The researchers propose that chromosomes exist in an intricate network of interactions, which are specific for each cell type, and which result in interactions between genes of different chromosomes. Identification and study of these physical contact points will help scientists to better understand gene regulation in processes as diverse as cancer or human evolution.

The human genome consists of 50,000 to 100,000 genes located within long strands of DNA (like beads in a string) which make up the 23 pairs of chromosomes found in humans. And while the human genome project has helped us to understand better our genetic makeup, the path from the information contained in our genes to the final result, that is a human being, is still poorly understood. Chimpanzees share 96% of our genome but we are undoubtedly very different from them, and scientists believe that much of these differences result from different gene interactions and regulatory mechanisms that allow some genes to be expressed but not others. But how does this happen? Part of the answer to this question, seems to lie in a period of the cellular life cycle called interphase. Interphase is the stage during which the cell is not dividing and is, instead, involved in high metabolic activity: genes are expressed (in a highly regulated manner) leading to the production of a variety of proteins that are found in the different cells in the body. It is also the period when many mutations occur during the duplication of the cell’s DNA material in preparation for cell division. During this phase each chromosome occupies a different area or territory in the nucleus. For a long time it has been believed that these territories were completely separate from each other, but recent data challenge this idea. In fact, not only have movements of chromosomes been observed during this stage, but also a large number of translocations takes place, implying some kind of chromosome proximity. Translocations are mutations which appear when two broken chromosomes are repaired incorrectly resulting in a broken chromosome piece inserted into the wrong chromosome

However, until now studies of the nucleus during interphase failed to show any significant amount of contact between chromosomes. But all this changed with the work of Branco and Pombo, which developed a technique capable of preserve much more efficiently chromosomes’ structure in the nucleus (destruction of chromosome structure turned out to be one of the problems in previous studies) while still allowing their clear visualization.

The researchers used this new technique to study cells of the human system and were amazed to find that chromosomes in these cells showed, contrary to all previous results, an extraordinary level of intermingling, with an average of 46% of each chromosome territory in contact with other chromosomes. Such level of juxtaposition between chromosomes immediately raised the possibility that this physical contact could have an important physiological function. Interestingly, Branco and Pombo also found that the degree of intermingling specific for each pair of chromosomes was directly related to the amount of translocations recorded for that pair. A chromosomal translocation is a potential disease-inducing process since the insertion of a chromosome piece into a different chromosome can lead to aberrant gene expression. This process is particularly dangerous when it affects oncogenes (genes with the potential to induce cancer) as it might lead to cancerous process including several types of leukaemia and lymphomas. The correlation between chromosome contact and translocation observed by Branco and Pombo is very interesting because it can explain, for example, why certain translocations, which can lead to cancer, appear only in some tissues. In fact, it is known that chromosome positioning in the nucleus is specific for each type of cells and consequently, probably also intermingling.

The next step was to understand if gene activity and intermingling were connected. To test this, Branco and Pombo decided to block a crucial step in gene expression only to find that this blocking also led to alterations in the intermingling levels supporting the existence of a link between the two processes. Next, the researchers did the reverse test and activated a gene, again looking for changes in intermingling. To their surprise they were able to clearly see the activated gene, getting into contact (intermingling) with three others chromosomes suggesting that the expression of the activated gene seems to involve some kind of interaction with these other chromosomes. These two experiments confirmed that intermingling is involved in gene expression and most probably not only in human cells.

Gene regulation is a key physiological mechanism. The expression of genes is known to be regulated at many levels but the way nuclear organisation can influence this process is perhaps the one about which less is known. Branco and Pombo’s work is a crucial step to understand this issue by supporting the existence of a network of chromosomes with multiple points of physical contact which creates a functional web, specific for each cell type, of communication between genes of different chromosomes.

There are many important implications for Branco and Pombo’s discovery. Observation of those contact points between chromosomes, by elucidating which areas (and genes) interact will be helpful in many different fields. These range from studies of human evolution and differential gene expression to causes of disease. A good example are cancers that result from abnormal regulation of an oncogene by other genes, that can start to be better understood as scientists become able to “see” exactly which chromosomes (and possibly genes) interact in patients.

Catarina Amorim | alfa
Further information:
http://biology.plosjournals.org/perlserv/?request=index-html
http://www.oct.mct.pt

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>