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A symmetric toggle switch explains the onset of random X inactivation in different mammals. | LitMetric

AI Article Synopsis

  • Gene-regulatory networks are essential for managing how genes express differently during development, especially when it comes to genes like Xist that have two copies.
  • The research focuses on understanding how mono-allelic expression of Xist—meaning only one copy is active—happens in female mammals, particularly during random X-chromosome inactivation (XCI).
  • By using mathematical modeling and experimentation, the study reveals that a symmetric toggle switch is key to achieving this mono-allelic expression, which helps explain variations seen in different species during XCI.

Article Abstract

Gene-regulatory networks control the establishment and maintenance of alternative gene-expression states during development. A particular challenge is the acquisition of opposing states by two copies of the same gene, as in the case of the long non-coding RNA Xist in mammals at the onset of random X-chromosome inactivation (XCI). The regulatory principles that lead to stable mono-allelic expression of Xist remain unknown. Here, we uncover the minimal regulatory network that can ensure female-specific and mono-alleleic upregulation of Xist, by combining mathematical modeling and experimental validation of central model predictions. We identify a symmetric toggle switch as the basis for random mono-allelic upregulation of Xist, which reproduces data from several mutant, aneuploid and polyploid mouse cell lines with various Xist expression patterns. Moreover, this toggle switch explains the diversity of strategies employed by different species at the onset of XCI. In addition to providing a unifying conceptual framework with which to explore XCI across mammals, our study sets the stage for identifying the molecular mechanisms needed to initiate random XCI.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558282PMC
http://dx.doi.org/10.1038/s41594-019-0214-1DOI Listing

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