Title |
A symmetric toggle switch explains the onset of random X inactivation in different mammals
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Published in |
Nature Structural & Molecular Biology, April 2019
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DOI | 10.1038/s41594-019-0214-1 |
Pubmed ID | |
Authors |
Verena Mutzel, Ikuhiro Okamoto, Ilona Dunkel, Mitinori Saitou, Luca Giorgetti, Edith Heard, Edda G. Schulz |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 16 | 23% |
United Kingdom | 8 | 11% |
Germany | 7 | 10% |
France | 6 | 9% |
Austria | 2 | 3% |
Switzerland | 2 | 3% |
Netherlands | 1 | 1% |
Australia | 1 | 1% |
New Zealand | 1 | 1% |
Other | 5 | 7% |
Unknown | 21 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 34 | 49% |
Scientists | 32 | 46% |
Science communicators (journalists, bloggers, editors) | 2 | 3% |
Practitioners (doctors, other healthcare professionals) | 2 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 75 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 15 | 20% |
Student > Ph. D. Student | 11 | 15% |
Student > Bachelor | 10 | 13% |
Researcher | 8 | 11% |
Other | 4 | 5% |
Other | 11 | 15% |
Unknown | 16 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 34 | 45% |
Agricultural and Biological Sciences | 12 | 16% |
Medicine and Dentistry | 3 | 4% |
Neuroscience | 2 | 3% |
Business, Management and Accounting | 1 | 1% |
Other | 5 | 7% |
Unknown | 18 | 24% |