Proteins called histones act as spools around which DNA winds, forming nucleosomes. The process of DNA wrapping is crucial for compactly packaging the enormous amount of genetic information within the limited space of cell nuclei. Disruptions to this packaging can lead to defects in gene expression and various diseases.
Using a cutting-edge technique known as cryo-electron microscopy, researchers have now obtained detailed three-dimensional images of nucleosomes. By manipulating DNA sequences and histone modifications, they identified key features that govern DNA wrapping. Their findings are reported in the journal Nature Communications.
"We uncovered important interactions that regulate how tightly DNA winds around nucleosomes. This improved understanding could lead to novel strategies to control DNA packaging and potentially correct gene expression abnormalities associated with diseases like cancer and developmental disorders," said Dr. Hiroshi Kimura, a postdoctoral researcher at the RIKEN Center for Biosystems Dynamics Research and the lead author of the study.
The research team used a type of cryo-electron microscopy called cryo-electron tomography, which enables the reconstruction of three-dimensional structures from frozen samples. This allowed them to observe nucleosomes in a near-native state within intact cells.
Their analysis revealed that the linker DNA connecting neighboring nucleosomes influences DNA wrapping. They found that long linker DNAs promote tighter DNA wrapping, while short linker DNAs result in looser winding.
"Our findings highlight the importance of considering linker DNA length in understanding nucleosome structure and function," said Dr. Kimura.
The researchers also discovered that certain histone modifications, particularly methylation of histone H3, affect DNA wrapping. This modification, which is often associated with gene silencing, loosens the DNA winding.
"These results provide new insights into how histone modifications regulate nucleosome dynamics and chromatin structure," said Dr. Hiroaki Shinkai, a senior researcher at the RIKEN Center for Biosystems Dynamics Research and the senior author of the study.
The team hopes that their findings will contribute to a deeper understanding of gene regulation and pave the way for developing therapeutic interventions targeting DNA packaging disorders.
