Abstract
The non-coding RNA Xist regulates the process of X chromosome inactivation, in which one of the two X chromosomes present in cells of early female mammalian embryos is selectively and coordinately shut down. Remarkably Xist RNA functions in cis, affecting only the chromosome from which it is transcribed. This feature is attributable to the unique propensity of Xist RNA to accumulate over the territory of the chromosome on which it is synthesized, contrasting with the majority of RNAs that are rapidly exported out of the cell nucleus. In this review I provide an overview of the progress that has been made towards understanding localized accumulation of Xist RNA, drawing attention to evidence that some other non-coding RNAs probably function in a highly analogous manner. I describe a simple model for localized accumulation of Xist RNA and discuss key unresolved questions that need to be addressed in future studies.
Highlights
X chromosome inactivation is the process that evolved in mammals to equalize levels of X-linked gene expression in XX females relative to XY males
This study further showed that Xist RNA dissociates from the chromosome at anaphase/telophase, with Xi-specific accumulation being re-established during early G1
The latter finding was based on fluorescence in situ hybridization (FISH) analysis using a probe specific for Xist RNA produced on the endogenous Xi
Summary
X chromosome inactivation is the process that evolved in mammals to equalize levels of X-linked gene expression in XX females relative to XY males. Integration of the inducible Xist transgene in female mouse embryo fibroblasts (MEFs) resulted in reduced Xist RNA clouds on an endogenous Xi chromosome (referred to as squelching), and, following transgene induction, Xist RNA from the Xi was detected in association with the transgene-expressing chromosome, indicating that Xist transcripts can localize to sites in trans The latter finding was based on FISH analysis using a probe specific for Xist RNA produced on the endogenous Xi. Further analysis identified a short region of Xist RNA centred on repeat F, which binds the nuclear protein YY1 and which is required for transgenic Xist RNA accumulation and squelching. Taking this uncertainty into consideration, in the context of this review I will focus on the generally held consensus that localized accumulation of Xist RNA over a defined chromosome territory occurs strictly in cis
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