ArticleAmerican journal of human genetics2001
Demethylation, reactivation, and destabilization of human fragile X full-mutation alleles in mouse embryocarcinoma cells.
Article in American journal of human genetics, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 124 citations in OpenAlex.
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- Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion.Science advances · 2020Article
- Repeat Instability in the Fragile X-Related Disorders: Lessons from a Mouse Model.Brain sciences · 2019Article
- The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS).Brain sciences · 2019Review
- The G-rich Repeats inGenetics · 2018Article
- Article
- FXS-Like Phenotype in Two Unrelated Patients Carrying a Methylated Premutation of theFrontiers in genetics · 2018Article
- Of Men and Mice: Modeling the Fragile X Syndrome.Frontiers in molecular neuroscience · 2018Article
- Review
- A Set of Assays for the Comprehensive Analysis of FMR1 Alleles in the Fragile X-Related Disorders.The Journal of molecular diagnostics : JMD · 2016Article
- CGG-repeat dynamics andMolecular autism · 2016Article
- The Repeat Expansion Diseases: The dark side of DNA repair.DNA repair · 2015Review
- Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas.Oncology letters · 2015Article
- Modeling diseases of noncoding unstable repeat expansions using mutant pluripotent stem cells.World journal of stem cells · 2015Review
- EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders.European journal of human genetics : EJHG · 2015Article
- CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles.Journal of medical genetics · 2014Article
- Gender and cell-type-specific effects of the transcription-coupled repair protein, ERCC6/CSB, on repeat expansion in a mouse model of the fragile X-related disorders.Human mutation · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The major causes of fragile X syndrome are mutational expansion of the CGG repeat in the FMR1 gene, hypermethylation, and transcriptional silencing. Most fragile X embryos develop somatic mosaicism of disease-causing "full" expansions of different lengths. Homogeneity of the mosaic patterns among multiple tissues in the same individual indicates that these previously unstable expansions acquire mitotic stability early in fetal life. Since mitotic stability is found strictly associated with hypermethylation in adult tissues, current theory has fixed the time of instability to developmental stages when fully expanded CGG repeats exist in an unmethylated state. We used murine embryocarcinoma (EC) cells (PC13) as a model system of pluripotent embryonic cells. Hypermethylated and unmethylated full expansions on human fragile X chromosomes were transferred from murine A9 hybrids into EC cells, by means of microcell fusion. As demonstrated in the present study for the first time, even full expansion alleles that were fully methylated and stable in the donors' fibroblasts and in A9 became demethylated, reactivated, and destabilized in undifferentiated EC hybrids. When destabilized expansions were reintroduced from EC cells into A9, instability was reversed to stability. Our results strongly support the idea that fully expanded alleles are initially unstable and unmethylated in the human embryo and gain stability upon genetic or epigenetic change of the embryonic cells.
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