Evidence map›Paper›PMID 27484239›Full record

ArticleeLife2016

Real-time imaging of Huntingtin aggregates diverting target search and gene transcription.

Li Li, Hui Liu, Peng Dong, Dong Li, Wesley R Legant, Jonathan B Grimm, Luke D Lavis, Eric Betzig, Robert Tjian, Zhe Liu

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
4.7field-weighted citation impact, top 5% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 107 citations in OpenAlex.

  1. Review
  2. Review
  3. GFP-free live neuron quantitative imaging reveals compartmentalization and growth dynamics of polyQ aggregates.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  4. Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders.Handbook of experimental pharmacology · 2026
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  7. Cell dynamics revealed by microscopy advances.Current opinion in cell biology · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.International journal of molecular sciences · 2024
    Review
  13. Article
  14. Article
  15. Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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  19. Rejuvenating old fluorophores with new chemistry.Current opinion in chemical biology · 2023
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Li LiJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.ORCID 0000-0002-2981-6615
Hui LiuJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Peng DongJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Dong LiJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Wesley R LegantJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Jonathan B GrimmJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Luke D LavisJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Eric BetzigJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Robert TjianJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.
Zhe LiuJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States.ORCID 0000-0002-3592-3150
Howard Hughes Medical Institute · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

The presumptive altered dynamics of transient molecular interactions in vivo contributing to neurodegenerative diseases have remained elusive. Here, using single-molecule localization microscopy, we show that disease-inducing Huntingtin (mHtt) protein fragments display three distinct dynamic states in living cells - 1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable aggregates of mHtt exclude chromatin and form 'sticky' decoy traps that impede target search processes of key regulators involved in neurological disorders. Functional domain mapping based on super-resolution imaging reveals an unexpected role of aromatic amino acids in promoting protein-mHtt aggregate interactions. Genome-wide expression analysis and numerical simulation experiments suggest mHtt aggregates reduce transcription factor target site sampling frequency and impair critical gene expression programs in striatal neurons. Together, our results provide insights into how mHtt dynamically forms aggregates and disrupts the finely-balanced gene control mechanisms in neuronal cells.

Indexed as

Protein Aggregation, PathologicalSingle Molecule ImagingTranscription, GeneticAnimalsCells, CulturedHuntingtin ProteinMiceMouse Embryonic Stem CellsMutant ProteinsNeuronsTranscription FactorsVisual CortexHtt protein, mouseHuntingtin ProteinMutant ProteinsTranscription Factorsbiophysicschromatinchromosomesgeneshuntingtin aggregatesmousestructural biologytranscription factors

Identifiers

PMID27484239
PMCPMC4972539
OpenAlexW2504778465

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.