An Essential Protein Complex has a Role in DNA Packing


A new study reported that an essential protein complex which breaks down proteins in cells, the proteasome, showed another surprising function, i.e., directly regulating the DNA packing in the nucleus. The study was led by scientists from the Korea Institute of Science and Technology and was published in the Journal of Biological Chemistry. 

The proteasome with proteolysis process breaks down proteins in the cell. Dysfunction in the proteasome occurs in diseases of many physiological systems, from the immune, nervous and cardiovascular systems to aging processes. The new study reported the ability of proteasome to perform additional functions apart from the proteolysis process.

In the nucleus DNA complexes with protein to form a structure called chromatin. Chromatin may occur as loosely packed chromatin/ euchromatin which allows DNA to be transcribed and genes to be expressed, or as tightly bound form (heterochromatin), which prevents gene expression.

Hogyu David Seo, a graduate student in Daeyoup Lee's lab, used yeast cells and showed that the proteasome induced heterochromatin formation in some parts of the genome and prevented the spreading the heterochromatin to other regions.  When the proteasome was mutated, he found that the proteasome’s effects on chromatin had no effect on proteolysis which indicated that the proteasome affects heterochromatin through an activity other than proteolysis. But the activity was not identified.

Seo said, "The proteasome can exert a force on proteins and translocate, tilt, bend them. So I believe the proteasome physically modulates proteins that act as a shield for heterochromatin. That's how I think it might work."

The alterations in the chromatin state of cells in one generation could be passed on to the next generation. Hence, heterochromatin formation and spread were important in the epigenetics field. 

"The proteasome may have some effect on epigenetic programming inheritance because it affects the spreading of heterochromatin. “I'm not sure how it might work because there are so many ways that it could act, but I'm sure that it may exert some effects on epigenetic programming," Seo added.

The researchers aimed to provide an insight into how the proteasome controls heterochromatin in organisms (yeast, mice and human cells).

Lee added that the proteasome engaged with each protein in our body for proteins degradation. Identifying of the proteasome functions would benefit the development of therapeutic approaches for various diseases, such as neurological diseases and cancer.