ArticleActa neuropathologica2014
C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD.
Article in Acta neuropathologica, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- Blood DNA methylation as a potential biomarker of dementia: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2018Pooled it
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- Integrative Multi-Omics Mendelian Randomization Highlights Causal Autophagy-Related Genes for Amyotrophic Lateral Sclerosis.Brain and behavior · 2026Article
- DNA methylation as a contributor to dysregulation of STX6 and other frontotemporal Lobar degeneration genetic risk-associated loci.Acta neuropathologica communications · 2025Article
- DNA methylation as a contributor to dysregulation ofbioRxiv : the preprint server for biology · 2025Article
- Analysis of C9orf72 repeat length in progressive supranuclear palsy, corticobasal syndrome, corticobasal degeneration, and atypical parkinsonism.Journal of neurology · 2025Article
- Review
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.Nature communications · 2025Article
- Epigenetics in Neurodegenerative Diseases.Sub-cellular biochemistry · 2025Review
- Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion.Molecular neurodegeneration · 2024Article
- Identification of selective and non-selectiveMolecular therapy. Nucleic acids · 2024Article
- DNA Methylation Profiles ofBiomedicines · 2024Article
- Review
- Genome-Wide DNA Methylation in Early-Onset-Dementia Patients Brain Tissue and Lymphoblastoid Cell Lines.International journal of molecular sciences · 2024Article
- Molecular hallmarks of ageing in amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2024Review
- Distinctive cell-free DNA methylation characterizes presymptomatic genetic frontotemporal dementia.Annals of clinical and translational neurology · 2024Article
- The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.American journal of human genetics · 2024Article
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.bioRxiv : the preprint server for biology · 2023Article
- Article
- Aberrant phase separation is a common killing strategy of positively charged peptides in biology and human disease.bioRxiv : the preprint server for biology · 2023Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Hexanucleotide repeat expansions of C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal degeneration. The mutation is associated with reduced C9orf72 expression and the accumulation of potentially toxic RNA and protein aggregates. CpG methylation is known to protect the genome against unstable DNA elements and to stably silence inappropriate gene expression. Using bisulfite cloning and restriction enzyme-based methylation assays on DNA from human brain and peripheral blood, we observed CpG hypermethylation involving the C9orf72 promoter in cis to the repeat expansion mutation in approximately one-third of C9orf72 repeat expansion mutation carriers. Promoter hypermethylation of mutant C9orf72 was associated with transcriptional silencing of C9orf72 in patient-derived lymphoblast cell lines, resulting in reduced accumulation of intronic C9orf72 RNA and reduced numbers of RNA foci. Furthermore, demethylation of mutant C9orf72 with 5-aza-deoxycytidine resulted in increased vulnerability of mutant cells to oxidative and autophagic stress. Promoter hypermethylation of repeat expansion carriers was also associated with reduced accumulation of RNA foci and dipeptide repeat protein aggregates in human brains. These results indicate that C9orf72 promoter hypermethylation prevents downstream molecular aberrations associated with the hexanucleotide repeat expansion, suggesting that epigenetic silencing of the mutant C9orf72 allele may represent a protective counter-regulatory response to hexanucleotide repeat expansion.
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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.