Silencing of one of the two X chromosomes in a female somatic cell brings the gene dosage level down to that of male cells. Inactivation is controlled by several noncoding RNAs transcribed from, and acting in cis upon, the X inactivation center (XIC). But the field has been perplexed as to how one chromosome knows what the other is doing to keep inactivation mutually exclusive.
The new results suggest that a prior meeting between X chromosomes sets the decision. Although mammalian chromosomes normally only pair during meiosis, the authors saw transient contact between X chromosomes just before the inactivation of one.
Pairing required only the gene sequences of two of the silencing RNAs. Addition of either of these sequences to an autosome drew X chromosomes away from each other and into autosomal pairings. Deletion of the sequences from the X chromosome also interfered with pairing and resulted in none, one, or both X chromosomes being inactivated.
The big next step for the field will be to identify the molecules behind this choice. Thinking on a larger scale, Lee imagines that other epigenetic events might also be preceded by transient chromosomal pairings. In support of this idea, close proximity in late S phase of the two copies of an imprinted locus has been reported.