ArticleNature structural & molecular biology2019
A symmetric toggle switch explains the onset of random X inactivation in different mammals.
Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 57 citations in OpenAlex.
- A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.RNA (New York, N.Y.) · 2026Article
- Graded versus ON/OFF control in quantitative gene expression and epigenetic memory.The EMBO journal · 2026Review
- Antisense transcription can induce expression memory via stable promoter repression.Genome biology · 2025Article
- Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.Nature structural & molecular biology · 2025Article
- Transcriptional stochasticity reveals multiple mechanisms of long non-coding RNA regulation at the Xist-Tsix locus.Nature communications · 2025Article
- Lineage-specific dynamics of loss of X upregulation during inactive-X reactivation.Stem cell reports · 2024Article
- Population variability in X-chromosome inactivation across 10 mammalian species.Nature communications · 2024Article
- Multifaceted role of CTCF in X-chromosome inactivation.Chromosoma · 2024Review
- Stepwise de novo establishment of inactive X chromosome architecture in early development.Nature genetics · 2024Article
- How does the Xist activator Rlim/Rnf12 regulate Xist expression?Biochemical Society transactions · 2024Review
- Establishment and maintenance of random monoallelic expression.Development (Cambridge, England) · 2024Review
- Stochasticity in genetics and gene regulation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Review
- Orchestrating Asymmetric Expression: Mechanisms behindEpigenomes · 2024Review
- IndiSPENsable for X Chromosome Inactivation and Gene Silencing.Epigenomes · 2023Review
- Population variability in X-chromosome inactivation across 9 mammalian species.bioRxiv : the preprint server for biology · 2023Article
- Regulatory principles and mechanisms governing the onset of random X-chromosome inactivation.Current opinion in genetics & development · 2023Review
- Species-specific regulation of XIST by the JPX/FTX orthologs.Nucleic acids research · 2023Article
- The Molecular and Nuclear Dynamics of X-Chromosome Inactivation.Cold Spring Harbor perspectives in biology · 2022Review
- Activation of Xist by an evolutionarily conserved function of KDM5C demethylase.Nature communications · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.