scholarly journals Acetylation Mimics Within a Single Nucleosome Alter Local DNA Accessibility In Compacted Nucleosome Arrays

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Laxmi N. Mishra ◽  
Sharon Pepenella ◽  
Ryan Rogge ◽  
Jeffrey C. Hansen ◽  
Jeffrey J. Hayes
Keyword(s):  
Dna Accessibility ◽  
Nucleosome Arrays

scholarly journals Inhibition of CRISPR-Cas12a DNA targeting by nucleosomes and chromatin

2021 ◽  
Vol 7 (11) ◽  
pp. eabd6030
Author(s):  
Isabel Strohkendl ◽  
Fatema A. Saifuddin ◽  
Bryan A. Gibson ◽  
Michael K. Rosen ◽  
Rick Russell ◽  
...  
Keyword(s):  
Histone Modifications ◽  
Dna Cleavage ◽  
Genome Engineering ◽  
Eukaryotic Cells ◽  
Loop Formation ◽  
Chromatin Compaction ◽  
Dna Targeting ◽  
Genomic Regions ◽  
Dna Bendability ◽  
Nucleosome Arrays

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.

scholarly journals Dynamics and function of compact nucleosome arrays

2009 ◽  
Vol 16 (9) ◽  
pp. 938-944 ◽  
Author(s):  
Michael G Poirier ◽  
Eugene Oh ◽  
Hannah S Tims ◽  
Jonathan Widom
Keyword(s):  
Dynamics And Function ◽  
And Function ◽  
Nucleosome Arrays

scholarly journals A Distinct Switch in Interactions of the Histone H4 Tail Domain upon Salt-dependent Folding of Nucleosome Arrays

2014 ◽  
Vol 289 (39) ◽  
pp. 27342-27351 ◽  
Author(s):  
Sharon Pepenella ◽  
Kevin J. Murphy ◽  
Jeffrey J. Hayes
Keyword(s):  
Tail Domain ◽  
Histone H4 ◽  
Nucleosome Arrays

scholarly journals Joint single-cell DNA accessibility and protein epitope profiling reveals environmental regulation of epigenomic heterogeneity

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Xingqi Chen ◽  
Ulrike M. Litzenburger ◽  
Yuning Wei ◽  
Alicia N. Schep ◽  
Edward L. LaGory ◽  
...  
Keyword(s):  
Single Cell ◽  
Environmental Regulation ◽  
Dna Accessibility

scholarly journals Revisit of Reconstituted 30-nm Nucleosome Arrays Reveals an Ensemble of Dynamic Structures

2018 ◽  
Vol 430 (18) ◽  
pp. 3093-3110 ◽  
Author(s):  
Bing-Rui Zhou ◽  
Jiansheng Jiang ◽  
Rodolfo Ghirlando ◽  
Davood Norouzi ◽  
K.N. Sathish Yadav ◽  
...  
Keyword(s):  
Dynamic Structures ◽  
Nucleosome Arrays

DNA STAINABILITY DEPENDS ON DNA QUANTITY AND DNA ACCESSIBILITY TO DYES

1991 ◽  
Vol 73 (2-3) ◽  
pp. 34a-34a
Author(s):  
Philippe Vago ◽  
Bernard Lamy
Keyword(s):  
Dna Accessibility

scholarly journals Dynamics of the nucleosomal histone H3 N-terminal tail revealed by high precision single-molecule FRET

2020 ◽  
Vol 48 (3) ◽  
pp. 1551-1571 ◽  
Author(s):  
Kathrin Lehmann ◽  
Suren Felekyan ◽  
Ralf Kühnemuth ◽  
Mykola Dimura ◽  
Katalin Tóth ◽  
...  
Keyword(s):  
Single Molecule ◽  
Histone H3 ◽  
Time Range ◽  
Histone H2a ◽  
Histone Tails ◽  
Dna Accessibility ◽  
Single Molecule Fret ◽  
Multiple Interaction ◽  
Nucleosome Disassembly ◽  
Dynamic Transitions

Abstract Chromatin compaction and gene accessibility are orchestrated by assembly and disassembly of nucleosomes. Although the disassembly process was widely studied, little is known about the structure and dynamics of the disordered histone tails, which play a pivotal role for nucleosome integrity. This is a gap filling experimental FRET study from the perspective of the histone H3 N-terminal tail (H3NtT) of reconstituted mononucleosomes. By systematic variation of the labeling positions we monitored the motions of the H3NtT relative to the dyad axis and linker DNA. Single-molecule FRET unveiled that H3NtTs do not diffuse freely but follow the DNA motions with multiple interaction modes with certain permitted dynamic transitions in the μs to ms time range. We also demonstrate that the H3NtT can allosterically sense charge-modifying mutations within the histone core (helix α3 of histone H2A (R81E/R88E)) resulting in increased dynamic transitions and lower rate constants. Those results complement our earlier model on the NaCl induced nucleosome disassembly as changes in H3NtT configurations coincide with two major steps: unwrapping of one linker DNA and weakening of the internal DNA - histone interactions on the other side. This emphasizes the contribution of the H3NtT to the fine-tuned equilibrium between overall nucleosome stability and DNA accessibility.

scholarly journals Distinct modes of DNA accessibility in plant chromatin

2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Huan Shu ◽  
Thomas Wildhaber ◽  
Alexey Siretskiy ◽  
Wilhelm Gruissem ◽  
Lars Hennig
Keyword(s):  
Dna Accessibility
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