Xist RNA expressed in male white-footed mice with only partial chromatin silencing, preprint finds

A preprint posted to bioRxiv from Cold Spring Harbor Laboratory describes findings in the white-footed mouse (Peromyscus leucopus) that challenge the long-held assumption that Xist expression is exclusive to female cells. The long noncoding RNA Xist is canonically responsible for initiating X-chromosome inactivation (XCI) in female eutherian mammals, coating one X chromosome and recruiting Polycomb-mediated chromatin silencing to equalise gene dosage between XX females and XY males.

The researchers report that male P. leucopus — which carry a single X chromosome — express Xist, but that this expression is associated with only restricted chromatin repression and incomplete dosage compensation of X-linked genes. This extends a growing body of evidence that Xist transcription in male cells is not simply aberrant or pathogenic, but may serve biological functions distinct from canonical XCI.

The findings add to fundamental questions about the evolution and mechanistic flexibility of dosage compensation across mammals. The results are from a preprint and have not yet undergone peer review; the findings should be interpreted with appropriate caution.