ArticleHuman molecular genetics2008
Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Altered DNA methylation and Dnmt expression in obese uterus may cause implantation failure.Journal of molecular histology · 2024Article
- A systematic scientometric review of paternal inheritance of acquired metabolic traits.BMC biology · 2023Review
- Article
- Gene-Environment Interactions in Repeat Expansion Diseases: Mechanisms of Environmentally Induced Repeat Instability.Biomedicines · 2023Review
- Suppression of trinucleotide repeat expansion in spermatogenic cells in Huntington's disease.Journal of assisted reproduction and genetics · 2022Article
- Expanded CAG/CTG repeats resist gene silencing mediated by targeted epigenome editing.Human molecular genetics · 2022Article
- Genetic and Epigenetic Interplay Define Disease Onset and Severity in Repeat Diseases.Frontiers in aging neuroscience · 2022Review
- Arsenic-induced epigenetic changes in cancer development.Seminars in cancer biology · 2021Review
- Epigenetic regulation in Huntington's disease.Neurochemistry international · 2021Review
- Mutation-selection balance and compensatory mechanisms in tumour evolution.Nature reviews. Genetics · 2021Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- Phenotypic variance in monozygotic twins with SCA3.Molecular genetics & genomic medicine · 2020Article
- Article
- Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion.Science advances · 2020Article
- The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias.Frontiers in neuroscience · 2020Review
- Open chromatin structure in PolyQ disease-related genes: a potential mechanism for CAG repeat expansion in the normal human population.NAR genomics and bioinformatics · 2019Article
- µLAS: Sizing of expanded trinucleotide repeats with femtomolar sensitivity in less than 5 minutes.Scientific reports · 2019Article
- Review
- Tandem repeats mediating genetic plasticity in health and disease.Nature reviews. Genetics · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Expanded CAG repeat tracts are the cause of at least a dozen neurodegenerative disorders. In humans, long CAG repeats tend to expand during transmissions from parent to offspring, leading to an earlier age of disease onset and more severe symptoms in subsequent generations. Here, we show that the maintenance DNA methyltransferase Dnmt1, which preserves the patterns of CpG methylation, plays a key role in CAG repeat instability in human cells and in the male and female mouse germlines. SiRNA knockdown of Dnmt1 in human cells destabilized CAG triplet repeats, and Dnmt1 deficiency in mice promoted intergenerational expansion of CAG repeats at the murine spinocerebellar ataxia type 1 (Sca1) locus. Importantly, Dnmt1(+/-) SCA1 mice, unlike their Dnmt1(+/+) SCA1 counterparts, closely reproduced the intergenerational instability patterns observed in human SCA1 patients. In addition, we found aberrant DNA and histone methylation at sites within the CpG island that abuts the expanded repeat tract in Dnmt1-deficient mice. These studies suggest that local chromatin structure may play a role in triplet repeat instability. These results are consistent with normal epigenetic changes during germline development contributing to intergenerational instability of CAG repeats in mice and in humans.
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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.