A symmetric toggle switch explains the onset of random X inactivation in different mammals
| Autor: | Edda G. Schulz, Ikuhiro Okamoto, Verena Mutzel, Luca Giorgetti, Ilona Dunkel, Edith Heard, Mitinori Saitou |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Systems biology Mutant Gene regulatory network Computational biology Biology Article X-inactivation 03 medical and health sciences 0302 clinical medicine Species Specificity X Chromosome Inactivation Structural Biology Animals Humans Gene Regulatory Networks Allele Molecular Biology Gene Alleles Murine cell 030304 developmental biology Mammals 0303 health sciences Systems Biology RNA Experimental validation Toggle switch Female RNA Long Noncoding XIST 030217 neurology & neurosurgery |
| Zdroj: | Nature Structural and Molecular Biology Nature Structural & Molecular Biology Nature structural & molecular biology |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/s41594-019-0214-1 |
| Popis: | SummaryGene-regulatory networks control 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 it is the case in mammals for Xist 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 uncovered the minimal Xist regulatory network, by combining mathematical modeling and experimental validation of central model predictions. We identified a symmetric toggle switch as the basis for random mono-allelic Xist up-regulation, which reproduces data from several mutant, aneuploid and polyploid murine 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 to explore X-chromosome inactivation across mammals, our study sets the stage for identifying the molecular mechanisms required to initiate random XCI. |
| Databáze: | OpenAIRE |
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