Skewed X inactivation in mammals

In an article just published in Genome Biology, Andrew Clark and his colleagues at Cornell describe an intriguing bias that they have found in transcription from the X chromosome.

In mammals, females have two X chromosomes whereas males only have one. This means that if expression from the two X chromosomes was equal, females would have twice as much gene product from the X chromosome, with potentially toxic results. To get around this, females only express genes from one of their X chromosomes and up until now it had been believed that the choice of which X chromosome is active and which is silenced is a random decision in placental mammals. Using a technique that allowed them to differentiate expression from the two X chromosomes, Clark’s group has used pyrosequencing to measure transcription in the brains of embryonic mice. They found a small but statistically significant preference for expression from the maternal chromosome, meaning that there is a slight bias towards inactivation of the paternal X. They speculate that this has so far gone undetected because of a lack of sufficiently sensitive methods.

It remains to be seen if this bias is observed in other tissues, or at other developmental stages, or in mammals other than mice, and the mechanism by which this bias occurs is still to be elucidated. Nevertheless, this is an exciting result that could potentially lead to a new way of understanding how dosage compensation is achieved in mammals.

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