Chromatin refers to a substance found within a chromosome that is composed of DNA and proteins. Histones are the major proteins found in chromatin. They help to package DNA in a compact format that fits into the cell nucleus. The Weizmann Institute of Science discovered a new mode of nuclear chromatin organization that was previously unknown in fully differentiated cells. This is where chromatin density is high in the nuclear periphery but undetectable at the nuclear center. It creates a centrally chromatin-devoid area.
Left: a 3D illustration of the nucleus representing the classical theory of DNA organization at its center. Right: A microscopic view of the nucleus in a fruit fly larva’s cell. The long chains of DNA (red), are attached to the nuclear lina (green), which is the inner layer of nuclear membrane. Image credit: Weizmann Institute of Science.
In an earlier study, Dr. Daria Amaiad-Pavlov (Weizmann Institute of Science) examined how mechanical forces affect cell nuclei in muscle cells and discovered evidence that muscle contractions have an immediate effect upon gene expression patterns.
” We couldn’t investigate this further as existing imaging methods depended on imaging chemically preserved cells. So they failed to capture the actual function of a working muscle.” Dr. Amiad Pavlov stated.
To address this issue, the researchers aimed to study muscle nuclei in live fruit fly (Drosophila) larvae.
They obtained images of the inner, linearly-organized complexes DNA and its proteins. These were surrounded by the membrane from the muscle nuclei.
Instead of filling the entire nucleus with chromatin molecules, the ‘noodles’, or long chromatin molecules were attached to the nucleus’ inner walls as a thin layer.
As a result of the interaction of oil and water, also known as phase separation (or phase separation), the chromatin separated from the bulk of liquid within the nucleus to find its place at its edges, while the majority of the fluid medium remained in the center.
The scientists realized they were well on their way to answering a fundamental biological question: How is chromatin and DNA organized in a nucleus of a living organism?
” But the results were so unexpected that we had to ensure no error had crept into and that this organization wasn’t universal,” stated Dr. Dana Lorber from the Weizmann Institute of Science.
The authors also created a theoretical model which included the physical factors that govern chromatin organization within the nucleus. These include the relative forces and attraction between chromatin, its liquid environment, and chromatin and nuclear membrane.
Their model predicted that the chromatin would undergo separation from its liquid phase depending on how much liquid is present in the nucleus. The phase separated chromatin could then be organized along the inside the nuclear membrane, just like they had observed in their experiments.
They also explained why chromatin appears to fill cell nuclei in prior studies.
” When scientists place cells on a glass plate to study their properties under a microscope they alter their volume and flatten them,” explained Professor Samuel Safran of Weizmann Institute of Science.
” This may cause some changes in the chromatin arrangement, and decrease the distance between its base .”
The team’s findings were published in the journal Science Advances.
Daria Amiad-Pavlov et al. 2021. Live imaging of chromatin distribution reveals novel principles of nuclear architecture and chromatin compartmentalization. Science Advances 7 (23); doi: 10. 1126/sciadv.abf6251
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