A long noncoding RNA influences the choice of the X chromosome to be inactivated.

X chromosome inactivation (XCI) is the process of silencing one of the X chromosomes in cells of the female mammal which ensures dosage compensation between the sexes. Although theoretically random in somatic tissues, the choice of which X chromosome is chosen to be inactivated can be biased in mice by genetic element(s) associated with the so-called X-controlling element (). Although the was first described and genetically localized nearly 40 y ago, its mode of action remains elusive. In the approach presented here, we identify a single long noncoding RNA (lncRNA) within the locus, Lppnx, which may be the driving factor in the choice of which X chromosome will be inactivated in the developing female mouse embryo. Comparing weak and strong alleles we show that Lppnx modulates the expression of , one of the key factors in XCI, by controlling the occupancy of pluripotency factors at Intron1 of . This effect is counteracted by enhanced binding of Rex1 in , another key element in XCI regulating the activity of Tsix lncRNA, the main antagonist of Xist, in the strong but not in the weak allele. These results suggest that the different susceptibility for XCI observed in weak and strong alleles results from differential transcription factor binding of Intron 1 and , and that represents a decisive factor in explaining the action of the .