For cellular gender equality, female cells silence one of their two X chromosomes. This silencing is initiated by the Xist RNA, which coats the chromosome from which it is expressed. In differentiating embryonic stem cells, the authors now show, this coating is rapidly followed by the exclusion of the transcription machinery.
The exclusion of RNA Pol II and transcription factors creates a transcription-free zone and is now the earliest event known to occur after Xist transcription. In fact, it happened even before several normally silenced X-linked genes were turned off. While still expressed, these genes were found on the periphery of the Xist zone, where they might reach polymerases.
When these loci were soon silenced, they repositioned to within the Xist domain. The timing of their movements suggests that transcription begins to shut down before a locus enters the domain. Local DNA reorganization appears to be necessary for their entry, as the Xist domain itself did not expand. Perhaps tethering to transcription factories prevents active loci from being internalized into the polymerase-free Xist environment.
The silencing of X-linked genes requires a conserved stretch of A-rich repeats in the Xist RNA. But the formation of the silent compartment was independent of these repeats, as was the silencing of repetitive X-chromosome sequences such as SINEs and LINEs within the Xist domain.
One model proposes that Xist RNA might create a zone that filters out transcription components and thereby silences the DNA that lies within, but Heard is not yet sure. “Is it that a nuclear compartment is created, and thus silencing happens,” she says, “or is it that silencing happens, and thus you've created a compartment?” Either way, she wonders whether autosomes take advantage of the Xist compartment to silence their own genes.