Genes can now be studied by bending DNA strands with light

In a groundbreaking study, scientists have discovered a way to manipulate the very fabric of life by using light to reshape DNA strands. This innovative approach provides new insights into the material properties of chromosomes, unlocking potential advancements in understanding gene expression and developing treatments for genetic diseases.

Chromatin, the material that makes up chromosomes, is a complex structure where long strands of DNA are wrapped tightly around proteins. Despite its compact nature, chromatin must unfurl in certain regions to allow cells to access and replicate genetic information.

Some areas remain rigid and coiled, silencing genes, while others are flexible and accessible, facilitating gene expression. This duality has led scientists to question whether chromatin behaves like a solid, a liquid, or a hybrid of both.

Answering this question is vital for advancements in disease treatment and cellular engineering. Chromatin’s material properties affect critical processes like transcription, replication, and genome protection. Yet, few tools exist to measure how chromatin reacts to forces or to study its physical characteristics at specific locations. A Princeton research team has now developed a revolutionary technique to address these gaps.

The ViscoElastic Chromatin Tethering and ORganization (VECTOR) system enables precise manipulation of chromatin loci. By inducing synthetic liquid-like droplets within the cell’s nucleus using a specific wavelength of blue light, researchers can apply controlled forces to targeted DNA sequences. This process causes rapid, precise repositioning of DNA strands in just a few minutes.

“Basically, we’ve turned droplets into little fingers that pluck on the genomic strings within living cells,” explained Cliff Brangwynne, a lead researcher on the project and director of Princeton’s Omenn-Darling Bioengineering Institute.

VECTOR builds on previous research involving biomolecular condensates, membraneless assemblies that form through liquid-liquid phase separation. These condensates, which resemble oil droplets in water, naturally occur in cells and play roles in functions like gene activation and chromatin remodeling.

By engineering condensates to attach to specific DNA loci, VECTOR utilizes the energy stored at these liquid interfaces to create capillary forces, effectively pulling DNA into new configurations.

The VECTOR system reveals that chromatin exhibits properties of both solids and liquids. This duality allows it to maintain structural integrity while remaining dynamic enough to support essential cellular functions. For example, VECTOR demonstrated that the elasticity of chromatin varies across different genomic regions, shedding light on the heterogeneity of chromatin’s viscoelastic nature.

In one experiment, researchers used VECTOR to pull two distant sections of a DNA strand together until they touched. This repositioning could potentially alter gene expression or regulation, opening new avenues for studying genome organization.

“We haven’t been able to have this precise control over nuclear organization on such quick timescales before,” said Brangwynne. The ability to manipulate DNA strands in real time offers unprecedented insights into how chromatin architecture influences cellular behavior.

The implications of VECTOR extend far beyond understanding chromatin mechanics. This technology could lead to innovative treatments for diseases rooted in genome misorganization, such as cancer. Unlike CRISPR, which edits DNA by cutting and altering sequences, VECTOR focuses on repositioning genes without modifying their sequences. This approach could help regulate protein imbalances linked to various diseases.

“If we can control the amount of expression by repositioning the gene, there is a potential future for something like our tool,” said Amy R. Strom, a postdoctoral researcher on the team.

Strom’s colleague, Yoonji Kim, added, “Our tool does not actually cleave the DNA sequences like CRISPR does.” Instead, VECTOR offers a gentler alternative for studying gene expression and cellular organization, paving the way for novel therapies that don’t involve permanent genetic alterations.

This precise control over chromatin positioning also has potential applications in high-throughput genomic studies. VECTOR’s ability to reposition telomeric and non-telomeric sequences, as well as entire nuclear bodies, makes it a versatile tool for mapping genome functionality and understanding nuclear dynamics.

By merging condensates and DNA manipulation, VECTOR combines insights from molecular biology and materials science. This interdisciplinary approach underscores the importance of physical forces within living cells. The interplay between chromatin and condensates reveals how the cell’s internal environment influences DNA organization and genome functionality.

The Princeton team’s findings, published in Cell, highlight the potential for natural condensates to perform mechanical work similar to molecular motors. These forces, measured in picoNewtons, arise from the energy stored in liquid interfaces. Such forces could help explain how chromatin is remodeled during processes like transcription and DNA repair.

“We can use this technology to build a map of what’s going on in there and better understand when things are disorganized like in cancer,” Strom said. With VECTOR, scientists can now probe chromatin’s mechanical properties with unprecedented precision, offering a clearer picture of how the genome is organized and regulated.

VECTOR represents a major leap forward in the field of genome science. By leveraging light-induced forces to manipulate DNA, this technology bridges the gap between molecular biology and biophysics. Its applications range from fundamental research to potential clinical therapies, offering hope for tackling diseases where genome misorganization plays a key role.

With VECTOR, researchers have unlocked a new dimension of cellular control, opening doors to discoveries that were once unimaginable. As scientists continue to explore the potential of this tool, its impact on the understanding of life’s blueprint promises to be profound.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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