Navigation Links
How chromosomes meet in the dark -- Switch that turns on X chromosome matchmaking
Date:12/26/2008

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.


'/>"/>

Contact: Dr Mario Nicodemi
M.Nicodemi@warwick.ac.uk
39-333-899-5996
University of Warwick
Source:Eurekalert

Related biology news :

1. Grant supports study of abnormal ring-shaped chromosomes
2. Fungi can tell us about the origin of sex chromosomes
3. Cold Spring Harbor Protocols features classic approaches for analyzing chromosomes
4. UGA researchers discover mechanism that explains how cancer enzyme winds up on ends of chromosomes
5. Exploding chromosomes fuel research about evolution of genetic storage
6. Keeping chromosomes from cuddling up
7. Switching goals
8. Researchers find signal that switches on eye development -- could lead to eye in a dish
9. Researchers identify how to switch off cancer cell genes
10. Leading cause of death in preemies might be controlled by resetting a molecular switch
11. Why the switch stays on
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/19/2017)... ALBANY, New York , April 19, 2017 /PRNewswire/ ... highly competitive, as its vendor landscape is marked by ... in the market is however held by five major ... and Safran. Together these companies accounted for nearly 61% ... majority of the leading companies in the global military ...
(Date:4/17/2017)... 17, 2017 NXT-ID, Inc. (NASDAQ: NXTD ... filing of its 2016 Annual Report on Form 10-K on Thursday ... ... available in the Investor Relations section of the Company,s website at ... website at http://www.sec.gov . 2016 Year Highlights: ...
(Date:4/13/2017)... According to a new market research report "Consumer IAM Market ... Authorization), Service, Authentication Type, Deployment Mode, Vertical, and Region - Global Forecast ... from USD 14.30 Billion in 2017 to USD 31.75 Billion by 2022, ... ... MarketsandMarkets Logo ...
Breaking Biology News(10 mins):
(Date:4/20/2017)... ... April 20, 2017 , ... Energetiq Technology , a ... that Chief Executive Officer (CEO) Debbie Gustafson has been appointed to the SEMI ... association connecting the electronics manufacturing supply chain. The mission of the SEMI NAAB ...
(Date:4/20/2017)... April 20, 2017 Dutch philosopher Koert van Mensvoort - ... at the University of Technology in Eindhoven - has written a ,Letter ... he calls on humanity to avoid becoming a slave and victim to its ... ... Dutch philosopher Koert van Mensvoort – founder of the Next Nature ...
(Date:4/19/2017)... ... April 18, 2017 , ... ... has been a key device for generating monodisperse droplets of known diameters for ... and for generating monodisperse solid particles by drying monodisperse droplets. , The ...
(Date:4/19/2017)... ... April 18, 2017 , ... ... Labs . The move comes after the company changed focus to making analytical ... new brand and our new technology,” says CEO Robert Hart. Founders Bernardo Cordovez, ...
Breaking Biology Technology: