ArticleProceedings of the National Academy of Sciences of the United States of America2014
Self-assembled FUS binds active chromatin and regulates gene transcription.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- A Systematic and Comprehensive Review on Disease-Causing Genes in Amyotrophic Lateral Sclerosis.Journal of molecular neuroscience : MN · 2020Pooled it
- Contrasting clinical trajectories in two ALS patients with rare FUS variants: implications for variant interpretation, penetrance, and trial readiness.Neurogenetics · 2026Article
- Mapping interactions between disordered regions reveals promiscuity in biomolecular condensate formation.Nature communications · 2026Article
- Degradation of G-quadruplex-binding proteins in chromatin using G4-ligand-based proteolysis-targeting chimeras.Nature chemistry · 2026Article
- Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS.Neurobiology of disease · 2026Article
- Cell Surface Vimentin Is an Attachment Factor That Facilitates Equine Arteritis Virus Infection In Vitro.Viruses · 2026Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Spuriously transcribed RNAs from CRISPR-sgRNA expression plasmids scaffold biomolecular condensate formation and hamper accurate genomic imaging.Nucleic acids research · 2025Article
- Dynamic properties of transcriptional condensates modulate CRISPRa-mediated gene activation.Nature communications · 2025Article
- G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes.Nucleic acids research · 2024Article
- The roles of FUS-RNA binding domain and low complexity domain in RNA-dependent phase separation.Structure (London, England : 1993) · 2024Article
- Review
- FUS-Mediated Inhibition of Myogenesis Elicited by Suppressing TNNT1 Production.Molecular and cellular biology · 2024Article
- Nicotinamide riboside, pterostilbene and ibudilast protect motor neurons and extend survival in ALS mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Copper toxicity and deficiency: the vicious cycle at the core of protein aggregation in ALS.Frontiers in molecular neuroscience · 2024Review
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- CRISPR-assisted transcription activation by phase-separation proteins.Protein & cell · 2023Article
- Location and Concentration of Aromatic-Rich Segments Dictates the Percolating Inter-Molecular Network and Viscoelastic Properties of Ageing Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Phase-separated DropCRISPRa platform for efficient gene activation in mammalian cells and mice.Nucleic acids research · 2023Article
- FUS fibrillation occurs through a nucleation-based process below the critical concentration required for liquid-liquid phase separation.Scientific reports · 2023Article
31 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
4 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Fused in sarcoma (FUS) is a DNA/RNA binding protein and mutations in FUS cause a subset of familial ALS. Most ALS mutations are clustered in the C-terminal nuclear localization sequence of FUS and consequently lead to the accumulation of protein inclusions in the cytoplasm. It remains debatable whether loss of FUS normal function in the nucleus or gain of toxic function in the cytoplasm plays a more critical role in the ALS etiology. Moreover, the physiological function of FUS in the nucleus remains to be fully understood. In this study, we found that a significant portion of nuclear FUS was bound to active chromatin and that the ALS mutations dramatically decreased FUS chromatin binding ability. Functionally, the chromatin binding is required for FUS transcription activation, but not for alternative splicing regulation. The N-terminal QGSY (glutamine-glycine-serine-tyrosine)-rich region (amino acids 1-164) mediates FUS self-assembly in the nucleus of mammalian cells and the self-assembly is essential for its chromatin binding and transcription activation. In addition, RNA binding is also required for FUS self-assembly and chromatin binding. Together, our results suggest a functional assembly of FUS in the nucleus under physiological conditions, which is different from the cytoplasmic inclusions. The ALS mutations can cause loss of function in the nucleus by disrupting this assembly and chromatin binding.
Indexed as
Identifiers
What OpenQuestion holds
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.