The work could lead to ways to counter the diseases linked to chromosome X girls and women.
Almost all girls and women on Earth takes almost two X chromosomes in each of their cells – but one has (mostly) nothing. This is because it has been silenced, keeping most of their DNA enclosed without reading like a book in a cage.
Left, a core of the male cell, in blue, shown in green coating RNA Xist the only X (white) chromosome that was not enough to silence the linked genes the X chromosome in red when researchers artificially treated to mute the single X. right, a female core cell, moreover, the lining Xist RNA silences genes on chromosomes X second target – because genes in first, and silent, X were able to assist the process.
Kalantry laboratory at the University of Michigan Medical School
Scientists thought they had discovered how cells do this, but new research from the University of Michigan Medical School shows the answer is not so clear.
And the findings could help lead to new ways of fighting disease linked to the X chromosome in girls and women – the kind that occur when the X chromosome that is read is misprints and defects.
In a new document in the Proceedings of the National Academy of Sciences , UM researchers show that a genetic molecule called Xist RNA is insufficient to silence the X chromosome gene for that molecule, Xist, it has been as the key factor in silencing one of the two X chromosomes in each female cell.
The findings come from the same team who recently appeared as a fragment of genetic material from reading Xist back, called an antisense RNA leads to the production of Xist RNA.
“Xist is widely to be both necessary and sufficient for X silencing believes” says Sundeep Kalantry team leader, Ph.D. “We have for the first time show that is not enough, there must be other factors, on the same chromosome X, then activating Xist and Xist RNA to cooperate with the X chromosome silencing”.
What’s more, Kalantry says, in the future it may be possible to change the level of these other factors in cells and activate the healthy copy, silenced a gene found on the X chromosome inactive.
More information about Xist
The Xist gene specific transcription abbreviation X-inactive, is located on each chromosome X. tells cells to produce a protein, as most genes do. Instead, Xist RNA produces physically covers all X-chromosome, and thus is believed to seal the most of the rest of the cellular world.
Now the U-M group has shown that Xist must have accomplices.
Although they are close to identifying these accomplices, they know that living in a very interesting place: the X chromosome that is intended to be silenced. While most genes on the inactive X chromosome are completely silenced, a handful of genes on the inactive X chromosome are made active.
It is this set of X inactivation ‘escapees’ the research team focused on chromosome. Since genes are expressed escapes both the active and inactive X chromosomes in women who produce more gene product in female cells in male cells, which have only a single X.
The laboratory study predicts Kalantry is this higher “dose” in women triggers selective X-inactivation in females; the lowest dose in men is insufficient.
That means that if researchers can pinpoint the factors that cause the inactivation of X to occur, could not find ways to affect the activity of genes on chromosomes X – specifically, the genes involved in certain diseases.
X marks the spot
A wide range of relatively rare diseases – as well as the relatively common conditions such as autism hemophilia and muscular dystrophy – are linked to problems with genes found on the X chromosome. Many of them have an impact on the thinking of an individual and the memory capacity and other aspects of cognition and intelligence.
“In women, we could imagine ‘wake up’ a healthy copy of a gene linked to the X chromosome in the inactive X chromosome, by modulating the dose of these genes called leaks and improving the effects of unhealthy copy , “says Kalantry.
Unfortunately, this approach probably will not help men with X-linked diseases, because they only have one X chromosome in each cell and inactivation of which would be detrimental.
But that’s exactly what made possible the new research: The team tried to mute the single X chromosome in males mother cells from turning Xist artificially mice. As a result, they could only silence the genes of chromosome X a little – because male cells had the X ‘twin’ chromosome to provide the necessary genes for silencing finish work.
When the researchers used female cells having an X already quenched – and therefore had the same number of active X and men chromosome – that were still able to silence the X activated when artificially turned Xist from that chromosome.
The difference was that the female cells had higher levels of products produced by the genes of leaks.
Now, Kalantry says, the team is focusing on genes escapes X-inactivation that enable specific first Xist RNA to be expressed and then work with Xist to be silenced.