ByJERUSALEM POST STAFF

Scientists from the Technion-Israel Institute of Technology have used "laser tweezers" to understand the structure of DNA better than ever before, shedding light on poorly understood mechanisms that influence how genes express themselves in the human body.

Chromatin is found in DNA, the essential code in the human body that provides instructions needed for function and development. Though there is said to be around two meters total of DNA in the human body, found in the nucleus of every single cell, it is compressed into just tens of microns in size. This is because of how DNA itself is packaged, formed into a compact structure known as chromatin.

Chromatin itself is organized by wrapping the DNA strands around a specific protein called histones. The spool-like structure it eventually forms is said to resemble beads on a string. These "strings" are then connected with a special type of histone called a linker histone, which helps the strands form into more complex structures called chromatosomes.

The advantage of packaging the human genome in this form is that it makes it possible for it to actually physically fit within the cell. However, it makes accessing it more difficult, which can pose problems for mechanisms within the cell that are supposed to read the DNA.

The result is that the way a gene is ultimately expressed becomes dependent on a particular method of packaging. How exactly this works is still a mystery, and scientists have struggled to find an answer. But one thing that has been uncovered is the role of linker histones in the organization of this packaging. In other words, if a linker histone malfunctions, it could lead to improper packaging, which can result in non-ideal gene expression.

According to some experts, it is believed that the end result of linker histone malfunctions could manifest as autism or serious diseases like cancer. But how the linker histones actually bind DNA in the first place remains a mystery, making it even more difficult to investigate the issue using conventional methods.

But an unconventional method is exactly what Dr. Sergei Rudnizky used. The scientist and his team developed a new method based on "optical tweezers," a method that uses a focused laser beam to capture individual molecules and exert force on them.The method itself was pioneered by Jewish-American scientist Arthur Ashkin in 1986. It was based on years of research he had conducted in the 1970s, which had later formed the basis for the 1986 work by Steven Chu on using optical tweezing on cooling and  trapping neural atoms. Chu would win the Nobel Prize in Physics for this in 1997, and would later go on to serve as US secretary of energy from 2009 to 2013. Ashkin himself would later win the Nobel Prize in Physics for it in 2018.The technology was also later employed in other sectors, and in 2010 was adopted by Tel Aviv University for nanotechnology research.With this laser tweezer, Rudnizky, under the supervision of Profs. Ariel Kaplan and Philippa Melamed were able to slowly detach one strand of DNA from the rest of the strands. The process functions in a manner similar to unzipping a zipper, slowly removing the strand from the chromatosome. It isn't a smooth process though, as the DNA strand can get stuck if it makes even the slightest contact with a histone. When that happens, more force is applied to advance further.

And as it turns out, histone-DNA contact is far more extensive, with chromatosomes being much larger than was previously believed. The linker histones themselves were also surprisingly flexible in structure because there were two different shapes the chromatosome can shift between, a symmetric and compact one and a relaxed and asymmetric one.

But it is possible to externally control the transition between these shapes through transcription mechanisms in the cells.

As suggested in the findings, published in the academic journal Molecular Cell, it is possible that the cell utilizes this transition to regulate its access to the DNA.

These findings are extremely significant, as they shed light on poorly understood functions of genome expression, which can further knowledge on the role of chromatin and chromatosomes in health and diseases.