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In the spotlight: X chromosome inactivation

Date:
August 18, 2015
Source:
Radboud University
Summary:
Each cell in a woman's body contains two X chromosomes. One of these chromosomes is switched off, because nobody can live with two active X chromosomes. Researchers have now shown the mechanism of spreading of this inactivation over the X chromosome.
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A nice example of X inactivation can be observed in the fur of tortoiseshell and calico cats. The gene for fur coloration resides on the X chromosome, while each of the two X chromosomes codes for a different color: black or orange. In an orange 'patch', only the X chromosome encoding the orange color is active, while in the black 'patches', only the X chromosome encoding the black color is active.
Credit: Image courtesy of Radboud University

Each cell in a woman's body contains two X chromosomes. One of these chromosomes is switched off, because nobody can live with two active X chromosomes. Hendrik Marks and Henk Stunnenberg, molecular biologists at Radboud University Nijmegen, have shown the mechanism of spreading of this inactivation over the X chromosome, together with the group of Joost Gribnau from Erasmus MC in Rotterdam. The scientific journal Genome Biology will publish the results.

In terms of sex chromosomes, men have a single X chromosome as well as an Y chromosome, whereas women have two copies of the X chromosome. A process called X inactivation makes sure that one of these X chromosomes becomes inactivated in females during early embryonic development. A random process determines which of the two is switched off.

Xist 'jumps'

During normal embryo development, X inactivation in females takes place at a very early stage. Others had already discovered that the molecule 'Xist' is key during X inactivation. In order to further study this process, Marks and his colleagues used embryonic stem cells as a model system to study X inactivation. With the latest technology, they were able to keep the two X chromosomes apart and measure one of them -- with its 166 million base pairs -- in detail. Every day they checked which parts of the chromosome had been switched off. "The whole process took about eight days," Marks explains "and the inactivation spreads out from the centre of the X chromosome towards the ends. That doesn't happen gradually but moves jumpwise from domain to domain."

Domains

"Domains are long pieces of DNA that cluster together in knots. As X inactivation jumps from domain to domain, we now know that these domains are co-regulated. It is very likely that diseases that are linked to incorrect inactivation of the X chromosome are due to improper spreading across domains."

Future plans

After one of the X chromosomes has been inactivated, it will stay inactive forever. In the future, Marks hopes to discover why sometimes the one while in other cases the other X chromosome is inactivated during development. That could help in treating X-linked diseases -- like Rett syndrome and fragile X syndrome. "Reactivating (part of) the 'right' X chromosome could be a potential treatment for these diseases. So the next step is to figure out how to do that."


Story Source:

Materials provided by Radboud University. Note: Content may be edited for style and length.


Journal Reference:

  1. Hendrik Marks, Hindrik H. D. Kerstens, Tahsin Stefan Barakat, Erik Splinter, René A. M. Dirks, Guido van Mierlo, Onkar Joshi, Shuang-Yin Wang, Tomas Babak, Cornelis A. Albers, Tüzer Kalkan, Austin Smith, Alice Jouneau, Wouter de Laat, Joost Gribnau, Hendrik G. Stunnenberg. Dynamics of gene silencing during X inactivation using allele-specific RNA-seq. Genome Biology, 2015; 16 (1) DOI: 10.1186/s13059-015-0698-x

Cite This Page:

Radboud University. "In the spotlight: X chromosome inactivation." ScienceDaily. ScienceDaily, 18 August 2015. <www.sciencedaily.com/releases/2015/08/150818112615.htm>.
Radboud University. (2015, August 18). In the spotlight: X chromosome inactivation. ScienceDaily. Retrieved May 28, 2017 from www.sciencedaily.com/releases/2015/08/150818112615.htm
Radboud University. "In the spotlight: X chromosome inactivation." ScienceDaily. www.sciencedaily.com/releases/2015/08/150818112615.htm (accessed May 28, 2017).

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