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 Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State

nachricht New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>