Sex chromosomes differentiate men from women. A woman carries two X chromosomes, whereas men carry only one X chromosome. If both the X chromosomes, and all the DNAs on them, were activated in women, they would develop double the amount of proteins as men, resulting in an imbalance that would destroy the biochemical balance of the females. A team of researchers, led by Anton Wutz, Professor of Genetics at ETH Zurich, have discovered several hundreds of ribonucleic acid (RNA) molecules called ‘Xist’ that are involved in the complete inactivation of one of the X chromosomes while females are still in the womb – a mechanism previously unknown.

Missing Answer: How X Chromosomes In Females Get Inactive

Hundreds of Xist molecules latch themselves onto one of the X chromosomes, attaching themselves to other molecules which result in the inactivation of the chromosome.

To study this in detail, scientists used stem cells derived from mice. These cells featured two specific characteristics: they had just one of each chromosome (similar to an unfertilized egg) and they were scientifically modified to continuously produce Xist RNA molecules. The latter, caused the inactivation of the single X chromosome, leading to cell death, since the particular genes required for continued survival could not be expressed.    

Following this discovery, scientists performed a large-scale screening experiment to identify which genes were vital for the X inactivation. They used a virus that caused random damage to individual genes in many of the modified stem cells. Cases where the virus destroyed a gene important for Xist RNA molecules to inactivate X chromosomes, no inactivation took place and the cell survived.

Isolating the cells that had managed to survive the previous experiment, scientists identified seven genes essential to X inactivation. One of these genes was ‘Spen’. It is a known fact that Spen expresses a protein that facilitates its binding to RNA, preventing genes from being read. Researchers have now shown that a cell lacking the Spen gene fails to accumulate enough proteins for efficiently binding to and altering the structure of the chromosome. Further research into the details of this process is still required.

Similar Studies Corroborate The Findings

Anton Wutz, Professor of Genetics at ETH Zurich stated that methodological advances in the past few years have facilitated this type of extraordinary research. To be able to study underlying phenomenon using stem cells with a simple set of chromosomes (created by the researcher five years ago at Cambridge University) is truly remarkable.

The findings have been published in the journal Cell Reports. The issue also features similar findings by British researchers. Using RNA interference, they discovered several genes involved in X activation, one of which was Spen.

Slight Difference In Mice And Humans

Genes expressing Xist and Spen are present in humans as well. Thus, the findings can be translated to human systems – at a theoretical level at least.

Moreover, French researchers have claimed that besides Xist, there is another X inactivation mechanism found exclusively in humans. Hence, interplay of inactivating and activating factors makes understanding the regulation of X chromosomes difficult and complicated.