Related Experiment Video
Updated: Jun 13, 2026
05:58
In Situ Nucleosome Assembly for Single-Molecule Correlative Force and Fluorescence Microscopy
Published on: September 6, 2024
Single-molecule nucleosome spacing coordinates chromatin fiber interactions.
Kaite Zhang1,2, Maria Julia Maristany3, Jan Huertas3,4
1Tetrad Graduate Program, UC San Francisco, San Francisco, CA.
Biorxiv : the Preprint Server for Biology
|June 12, 2026
Summary
Chromatin fibers with similar nucleosome spacing interact more in 3D, a pattern called fiber homotypy. This finding reveals how nucleosome patterns guide higher-order chromosome structure in cells.
Area of Science:
- Genomics
- Molecular Biology
- Structural Biology
Background:
- Nucleosome spacing is known to influence chromatin organization in vitro.
- Its role in cellular chromosome structure remains debated.
- Understanding this link is crucial for deciphering genome organization.
Purpose of the Study:
- To develop a method for measuring nucleosome spacing patterns and their 3D interactions in cells.
- To investigate the relationship between nucleosome spacing and higher-order chromatin structure genome-wide.
- To uncover the mechanisms regulating chromatin fiber interactions.
Main Methods:
- Developed Ligation Analysis of Single-molecule Sequence Interactions (LASSI), a single-molecule epigenomic technique.
- LASSI combines proximity ligation with adenine methyltransferase footprinting for near-nucleotide resolution.
- Applied LASSI to mouse embryonic stem cells (mESCs) for genome-wide analysis.
Main Results:
- Discovered a genome-wide pattern termed 'fiber homotypy,' where similar nucleosome spacing patterns lead to increased 3D interactions.
- Observed that fiber homotypy is promoted by TADs, A/B compartments, and shared histone modifications.
- Molecular dynamics simulations showed heterogeneous nucleosome spacing regulates homotypy and compartmentalization.
Conclusions:
- Shared nucleosome spacing patterns drive fiber-fiber interactions, instructing higher-order chromosome organization.
- Demonstrated structural interdependence across cellular chromatin length scales.
- Showed loop extrusion antagonizes fiber homotypy, with cohesin levels modulating this effect.
More Related Videos
Related Concept Videos
02:21Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
01:32Chromatin Packaging
Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
02:21Chromatin Packaging
Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter?
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order structures.
02:54Nucleosome Remodeling
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
01:19The Nucleosome
Human DNA is almost two meters long. However, it is compressed inside a tiny nucleus measuring only a few microns in diameter. To make this degree of compaction possible, DNA is organized into several sequential levels so that it can fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
In a chromosome, DNA is wound twice around a protein complex called a histone octamer core, which consists of 8 histone proteins. This...
02:33The Nucleosome
DNA in a human cell is almost 2m long and it is packed inside a tiny nucleus that is only a few microns in diameter. The level of compaction of DNA inside the nucleus is astonishing. It is organized into several sequentially higher levels of compaction to fit into such a tiny space. The most compact form of DNA is a chromosome that can be seen under a microscope in a dividing cell.
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...
DNA is wound twice around a protein complex called histone core, that consist of 8 histone proteins. This complex...