The Xic region needs to sense the number of X chromosomes in the cell, count the X-to-autosome ratio and then choose which X chromosome to inactivate. The first steps in X-chromosome inactivation (XCI) are triggered when
Xist
is monoallelically upregulated from one of the two Xics on the future inactive X and
Tsix
is downregulated, thereby kick-starting the shut down of one chromosome. For this monoallelic regulation to happen, the two Xist/Tsix loci need to interact with each other. But there is evidence that these Xic functions are not sufficient to initiate XCI — for example, a Xist/Tsix-containing single-copy transgene alone cannot initiate XCI. In fact, there was evidence that some other Xic element, acting in trans, is also involved.
The authors looked for such trans-pairing elements using DNA fluorescence in situ hybridisation — BAC probes spanning the 800 kb mouse Xic region were applied to mouse ES cells that were either undifferentiated or differentiating to see whether any of the probes hybridized to the Xic region in early but not late cells. One region, called Xpr (for X-pairing region), met these criteria — this element lies ∼200 kb upstream of Xist and can mediate interactions between X chromosomes, even when inserted as a single-copy transgene. Importantly, this homologous association occurs before the onset of X inactivation and independently of the Xist–Tsix interactions.
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