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The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome

Wednesday, July 10, 2013

Science DOI: 10.1126/science.1237973


It's been known for some time that the RNA called Xist is responsible for turning off one of the two X chromosomes that are present in every cell in females of our species (and many other species too). Xist wraps copies of itself around one of the X chromosomes in each cell of a female and prevents expression of genes from that chromosome, so that only one of the two X chromosomes contributes to the cellular function -- this is how calico cats happen, since the X chromosome encodes color proteins in the cat genome, and a cat with two X chromosomes coding for different color proteins will have only one of those two X chromosomes being active in any given cell in its body, resulting in the mosaic/calico appearance from having different color proteins expressed in different cells in the cat's body.


What was not known is how the Xist RNA wraps multiple copies of itself (it is small relative to the large X chromosome) around one of the X chromosomes to shut it down. Jesse's work shows that the Xist RNA spreads across the X chromosome sheerly by 3D proximity -- that is, it spreads to whatever parts of the genome are touching it physically in 3D space -- rather than spreading by recognizing specific motifs in the genome to which it preferentially binds. It's really cool stuff! And on top of this, he came up with a experimental method by which researchers can identify where in the genome any given RNA is bound, allowing for the future study of the localization of other RNAs like Xist.  Read more ...