Related Experiment Video
Updated: Jun 30, 2026
10:40
Assembly of Nucleosomal Arrays from Recombinant Core Histones and Nucleosome Positioning DNA
Published on: September 10, 2013
DNA Sequence and Histone Variant H2A.Z Jointly Govern Nucleosome Unwrapping Pathways.
Abhik Ghosh Moulick1, Rutika Patel1,2, Tania Rajpersaud1,2
1Department of Chemistry, College of Staten Island, City University of New York, 2800, Victory Blvd., 6S-238, Staten Island, NY 10314.
Biorxiv : the Preprint Server for Biology
|June 29, 2026
Summary
Nucleosome unwrapping directionality is controlled by DNA sequence and histone variants. The H3 tail disengaging from DNA acts as a switch, and H2A.Z histone variant substitution reverses this preference.
Area of Science:
- Molecular Biology
- Biophysics
- Computational Biology
Background:
- Nucleosome unwrapping is crucial for chromatin accessibility and gene regulation.
- The molecular mechanisms dictating nucleosome unwrapping directionality are not well understood.
Purpose of the Study:
- To investigate the roles of DNA sequence and histone variant composition in determining nucleosome unwrapping directionality.
- To elucidate the molecular determinants that switch unwrapping preference.
Main Methods:
- Atomistic and SIRAH coarse-grained umbrella sampling simulations were employed.
- Investigated DNA sequences (ASP, Widom-601) and histone variants (canonical H2A vs. H2A.Z).
Main Results:
- Both DNA sequence and histone variant composition jointly influence unwrapping directionality.
- H3 N-terminal tail disengagement acts as a molecular switch for directionality in the Widom-601 system.
- Substitution of H2A with H2A.Z reverses unwrapping directionality and alters the free energy landscape.
Conclusions:
- H3 tail-DNA disengagement is a key determinant of nucleosome unwrapping directionality.
- Histone variant substitution (H2A.Z) can reverse unwrapping preference.
- SIRAH coarse-grained simulations are validated as an efficient tool for chromatin simulations.
Related Concept Videos
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Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
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The paradox
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The paradox
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their main responsibility is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. While on the other hand, they must allow polymerase enzymes to access DNA...
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Acetylation
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Acetylation
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Acetylation
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