Expansion microscopy unlocks genome secrets in cells

Chromatin expansion microscopy reveals nanoscale transcription and chromatin organization.

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The process of gene transcription is essential for cell diversity, human development, and health and disease. It entails transferring knowledge from our DNA‘s “carbon copy,” known as RNA, into RNA. 

Traditional microscopy techniques have limitations, but a revolutionary microscopy method has allowed researchers to witness molecular processes in genetic material that had never been observed before, giving them invaluable insights into how genes are activated and regulated.

Harvey and Kate Cushing, Professor of Cell Biology and Professor of Biomedical Engineering and Physics, Joerg Bewersdorf, Ph.D., and Antonio Giraldez, Ph.D., worked together to create the new method known as chromatin expansion microscopy (ChromExM).

They described how they successfully increased the physical volume of the zebrafish embryonic cells’ nucleus by 4,000 times in a report published online in Science on July 6. With this technology, scientists created a novel model of how genes are controlled and observed for the first time how certain chemicals influence gene expression in cells during embryonic development.

Giraldez from yale university said, “Our research allows us to see fundamental processes in the nucleus that are the basis for everything in life, from the making of an embryo to cancer,” “We can see processes that we could only imagine before.”

They can now observe fundamental nuclear processes that underlie everything in life, from the development of an embryo to the development of cancer. Processes that were previously only imaginable are now visible.

Since starting their investigation into how the genome is turned on, Giraldez and his team have made tremendous progress in identifying key players and understanding which genes are activated. However, they had never personally witnessed the genome activating. The team observed the genome’s essential functions for the first time thanks to ChromExM. As a result, scientists created a novel gene regulation theory called “kiss-and-kick.”

The team is eager to test theories that were previously untestable using ChromExM. They intend to investigate, for instance, how specific genes are activated or deactivated, how they are positioned in relation to one another in the nucleus, and how mutations influence gene locations. Furthermore, ChromExM is affordable for most laboratories, whereas other microscopy methods could be prohibitively expensive.

The group is currently working to enhance the technique’s resolution even more. Even though scientists can now see chemicals interacting with the genome, they are still unable to pinpoint specific genes. They seek a camera that will enable researchers to concentrate on specific individuals to comprehend better the underlying principles of how genes are activated and deactivated, damaged or repaired, and how mutations affect their function. 

This information will help researchers comprehend the fundamental ideas underlying how genes are activated and deactivated, destroyed or repaired, and how mutations alter their function. These are crucial first steps towards comprehending how our genes function in health and sickness.

Journal Reference:

  1. Mark E. Pownall,Charles E. Vejnar, etal. Chromatin expansion microscopy reveals the nanoscale organization of transcription and chromatin. Science. DOI: 10.1126/science.ade5308
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