Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How chromosomes meet in the dark - Switch that turns on X chromosome matchmaking

30.12.2008
A research group lead by scientists at the University of Warwick has discovered the trigger that pulls together X chromosomes in female cells at a crucial stage of embryo development.

Their discovery could also provide new insights into how other similar chromosomes spontaneously recognize each other and are bound together at key parts of analogous cell processes. This is an important mechanism as the binding togetgher of too many of too few of a particular chromosome can cause a number of medical conditions such as Down’s Syndrome or Turner’s Syndrome.

In our cells most genes are expressed from both types of each chromosome linked gene, but the most notable exception to this rule are X-linked genes in female mammals. During embryo development, in a step necessary to survival, one of the X chromosomes is silenced in each female cell to ensure that the levels of X-derived products are equalized in XX females and XY males, via a process known as X-Chromosome Inactivation (XCI). Recent discoveries have revealed that for that stage in the process to happen the X chromosomes have to quickly pair off (or colocalize) in a way that allows each part of those pairs of X chromosomes to be very close together and be aligned in a particular way. Failure to achieve this close physical colocalization of the two X chromosomes will lead to XCI failure and cell death.

Chromosome colocalization events are common in cells. A prominent example being mesiosis: for sexual reproduction to succeed in producing viable cells all of the homologous chromosomes in the process have to, almost simultaneously, bind together in pairs.

Yet until now the mechanisms of chromosome self-recognition and colocalization remain deeply mysterious. Researchers have had no clear understanding of how the X chromosomes actually suddenly pair off so quickly and consistently allowing this to happen.

Dr Mario Nicodemi, from the Department of Physics at the University of Warwick and Dr Antonio Scialdone from the University of Naples have uncovered exactly how this process is switched on and published their findings in PLOS in a paper entitled Mechanics and Dynamics of X-Chromosome Pairing at X Inactivation.

University of Warwick physicist Dr Mario Nicodemi, has recently published research on just how one X chromosome is able to silence another as part of the XCI process. However for that stage in the process to happen the X chromosomes have to quickly pair off (colocalization) in a way that allows each part of those pairs of X chromosomes to be very close together and aligned in a particular way.

In this latest paper the Warwick and Naples researchers looked at a particular “DNA specific binding molecule” including a protein known as CTCF that seemed to play a role in pairing off of X chromosomes. In the past when other researchers had mutated CTCF, or deleted the sections of DNA that the CTCF bound to, they found that it disrupted the pairing up or colocalization of the X Chromosomes. Clearly then CTCF had a role to play in the process but it was not obvious how it did so with the precise timing and speed required.

Obviously sheer chance meant that CTCFs would randomly encounter and bind to an X chromosome. There was an even smaller probability then that such a pairing would then encounter another X chromosome and bind to it as well – the CTCF would effectively then force colocalization by this unlikely double chance encounter, forming a chemical bridge between the two chromosomes. However such a gradual chance based occurrence did not fit with the speed and efficiency of how the actual process of colocalization of the X chromosomes really happened during XCI.

The Warwick lead research team created a model of the interaction between X chromosomes and CTCF proteins using polymer physics. They looked at models of chains of polymer beads that had almost the same number of chemical binding sites on their beads as the number of known CTCF binding sites in the key part of X chromosomes.

Their simulations using this system found that in that a key tipping point was reached if the amount of CTCF present in the system reached a critical threshold - a concentration of around 0.1 mg per millilitre or less. Below that point very little happened. Random bindings did occur but not often enough or quickly enough to build the sort of momentum necessary to produce the total and sudden of X Chromosomes colocalization required for successful X inactivation.

However once the threshold concentration is reached it produces a tipping point or thermodynamic switch. That particular concentration of CTCF was suddenly enough to ensure that the CTCF proteins could encounter and bind in quick succession to two X chromosomes forming a chemical bridge between them and almost instantly bringing about colocalization of the X chromosomes and making embryo development successful.

The researchers believe that this newly discovered “thermodynamic switch” not only explains how X chromosomes pair up during meiosis but also apply to a range of other cell processes that involve the recognition and pairing of DNA sequences including other homologous chromosomes. This is of particular importance, e.g., at meiosis, as the binding of togetgher of too many or too few of a particular chromosome can cause a number of medical conditions.

Peter Dunn | alfa
Further information:
http://www.warwick.ac.uk

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

Study shows how water could have flowed on 'cold and icy' ancient Mars

18.10.2017 | Physics and Astronomy

Navigational view of the brain thanks to powerful X-rays

18.10.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>