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Journal Article

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

MPS-Authors
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Mutzel,  Verena
Regulatory Networks in Stem Cells (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Dunkel,  Ilona
Regulatory Networks in Stem Cells (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Schulz,  Edda G.
Regulatory Networks in Stem Cells (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Fulltext (public)

Mutzel2019.pdf
(Publisher version), 3MB

Supplementary Material (public)

41594_2019_214_MOESM1_ESM.pdf
(Supplementary material), 4MB

41594_2019_214_MOESM3_ESM.xlsx
(Supplementary material), 21KB

Citation

Mutzel, V., Okamoto, I., Dunkel, I., Saitou, M., Giorgetti, L., Heard, E., et al. (2019). A symmetric toggle switch explains the onset of random X inactivation in different mammals. Nature Structural and Molecular Biology, 26(5), 350-360. doi:10.1038/s41594-019-0214-1.


Cite as: http://hdl.handle.net/21.11116/0000-0004-9918-5
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.