Normally, when a cell has two X-chromosomes (female genome), one is randomly inactivated. How does the cell detect that there are two X-chromosomes in the first place?

Is there some kind of protein that's coded in the X-chromosome, such that having two X's increases the protein concentration and a dosage effect causes one to become inactivated? I can't find any information about it in my textbook, nor on Google. A citation would be appreciated - especially for peer-reviewed research.


1 Answer 1


Even a male cell can count the number of X chromosomes. (Lee et al. 1996; Cell 86: 83-84)

When X inactivation is getting started the two chromosomes "kiss" - a process that lasts for a couple of hours (first shown by Jeannie Lee in 1996). The physical contact between two X chromosomes is over a small fraction of the chromosome but it's essential for triggering inactivation. (Xu et al. 2006: Science 311: 1149-52)

If it doesn't happen then the X chromosome assumes it's alone which would mean that Xist never gets switched on and inactivation never happens (a key stage in chromosome counting).

Chromosome counting is a process in which cells determine somehow their intrinsic chromosome number(s). The best-studied cellular mechanism that involves chromosome counting is 'chromosome-kissing' and X-chromosome inactivation (XCI) mechanism. It is necessary for the well-known dosage compensation between the genders in mammals to balance the number of active X-chromosomes (Xa) with regard to diploid set of autosomes. At the onset of XCI, two X-chromosomes are coming in close proximity and pair physically by a specific segment denominated X-pairing region (Xpr) that involves the SLC16A2 gene.

Take a look at Xist and Tsix. Some more papers worth taking a look at: Xist regulation and function eXplored Mechanism of regulation of ‘chromosome kissing’ induced by Fob1 and its physiological significance

  • $\begingroup$ Please note that this only applies to placental mammals. Drosophila, for example, has a different method for compensating for the two copies of the XX chromosome in females. $\endgroup$
    – David
    Oct 25, 2021 at 20:53

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