Specialized chaperones

A n interphase meeting between X chromosomes, revealed by Na Xu, Chia-Lun Tsai, and Jeannie Lee (Harvard Medical School, Boston, MA), ensures that one and only one is silenced. 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 fi eld 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 fi eld 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.