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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>