ArticleScience advances2021
Inhibition of CRISPR-Cas12a DNA targeting by nucleosomes and chromatin.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
- Gigabase-scale deletion scanning of the human genome.bioRxiv : the preprint server for biology · 2026Article
- Operating CRISPR/Cas12a in a complex nucleic acid sequence background.Nucleic acids research · 2026Article
- Evaluating high-fidelity CRISPR-Cas nucleases in nucleosomal contexts using a quantitative framework.Frontiers in genome editing · 2026Article
- Ectopic Recruitment of the CTCF N-Terminal Domain with Two Proximal Zinc-Finger Domains as a Tool for 3D Genome Engineering.International journal of molecular sciences · 2025Article
- Post-cleavage target residence determines asymmetry in non-homologous end joining of Cas12a-induced DNA double strand breaks.Genome biology · 2025Article
- PAM-adjacent DNA flexibility tunes CRISPR-Cas12a off-target binding.Scientific reports · 2025Article
- Histone demethylases in autophagy and inflammation.Cell communication and signaling : CCS · 2025Review
- CRISPR-array-mediated imaging of non-repetitive and multiplex genomic loci in living cells.Nature methods · 2024Article
- Cas12a domain flexibility guides R-loop formation and forces RuvC resetting.Molecular cell · 2024Article
- Eukaryotic-driven directed evolution of Cas9 nucleases.Genome biology · 2024Article
- Transposons and CRISPR: Rewiring Gene Editing.Biochemistry · 2023Article
- acCRISPR: an activity-correction method for improving the accuracy of CRISPR screens.Communications biology · 2023Article
- Proximal binding of dCas9 at a DNA double strand break stimulates homology-directed repair as a local inhibitor of classical non-homologous end joining.Nucleic acids research · 2023Article
- The impact of nucleosome structure on CRISPR/Cas9 fidelity.Nucleic acids research · 2023Article
- Decorating chromatin for enhanced genome editing using CRISPR-Cas9.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Chromatin accessibility: methods, mechanisms, and biological insights.Nucleus (Austin, Tex.) · 2022Review
- Molecular organization of the early stages of nucleosome phase separation visualized by cryo-electron tomography.Molecular cell · 2022Article
- Targeted Modification of Mammalian DNA by a Novel Type V Cas12a Endonuclease fromInternational journal of molecular sciences · 2022Article
- Increased Gene Targeting in Hyper-Recombinogenic LymphoBlastoid Cell Lines Leaves Unchanged DSB Processing by Homologous Recombination.International journal of molecular sciences · 2022Article
- MARCKSL1-2 reverses docetaxel-resistance of lung adenocarcinoma cells by recruiting SUZ12 to suppress HDAC1 and elevate miR-200b.Molecular cancer · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Genome engineering nucleases must access chromatinized DNA. Here, we investigate how AsCas12a cleaves DNA within human nucleosomes and phase-condensed nucleosome arrays. Using quantitative kinetics approaches, we show that dynamic nucleosome unwrapping regulates target accessibility to Cas12a and determines the extent to which both steps of binding-PAM recognition and R-loop formation-are inhibited by the nucleosome. Relaxing DNA wrapping within the nucleosome by reducing DNA bendability, adding histone modifications, or introducing target-proximal dCas9 enhances DNA cleavage rates over 10-fold. Unexpectedly, Cas12a readily cleaves internucleosomal linker DNA within chromatin-like, phase-separated nucleosome arrays. DNA targeting is reduced only ~5-fold due to neighboring nucleosomes and chromatin compaction. This work explains the observation that on-target cleavage within nucleosomes occurs less often than off-target cleavage within nucleosome-depleted genomic regions in cells. We conclude that nucleosome unwrapping regulates accessibility to CRISPR-Cas nucleases and propose that increasing nucleosome breathing dynamics will improve DNA targeting in eukaryotic cells.
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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.