New Colorado State University Research Proves Histone Proteins in Cells Need Chaperones to Prevent ‘Hanky-Panky’

Chromatin proteins get their wires crossed and misbehave without a critical protein that acts as a chaperone, according to new research from Colorado State University appearing Friday in the journal “Molecular Cell.”

The collaborative research, spearheaded by University Distinguished Professor Karolin Luger and Professor Laurie Stargell in the Department of Biochemistry and Molecular Biology, proves for the first time that eliminating the histone chaperone nucleosome assembly protein 1, known as Nap1, in a yeast cell leads to the wrong types of interaction in the cell by chromatin proteins, which could lead to cancer and disease.

“There’s this group of proteins in each cell that are called chaperones and literally, it has always been proposed that what they do is what human chaperones do – prevent inappropriate interactions between partners and help make the right interactions,” said Luger, also a Howard Hughes Medical Investigator. “With this paper we’ve proven that this is really the case for this particular protein. The chaperones prevent hanky-panky between partners who like each other, but have no business being together.”

Cells without this chaperone don’t behave properly – their gene expression patterns are abnormal, which is one of the reasons they become mutant cells.

The discovery was made in vitro – in a test tube with isolated proteins, through meticulously measuring the strength of interactions between the chaperone and the chromatin proteins. The predictions made from these studies were then found to apply to the living cell: The Colorado State team discovered through this research that the four histone proteins that help organize DNA into cells into units called nucleosomes can form alternative structures if the histone chaperone is not allowed to do its job. That discovery may change the way scientists have to look at genome-wide maps of nucleosome position.

The nucleosome is a spool-like basic building block of chromatin, the material in which billions of DNA base pairs are compacted in an individual cell nucleus.

“There’s these ‘unusual’ chromatin structures that may have a role as well,” Luger said. “They are not structures that look like our regular nucleosomes. They may still exist in a certain part of the genome because no one has ever looked. People have probably seen them before and discounted them.

“Putting these two discoveries from two completely different experimental approaches together is actually very, very powerful – it really shows the strength of our department. This research is about understanding the healthy cell – you need to understand how a car works before you go and fix it.”

Other authors on the paper are Andrew Andrews and Xu Chen, post-doctoral fellows, and Alexander Zevin, an undergraduate student. A grant by the National Institutes of Health originally funded the research.

Luger is one of the world’s foremost authorities in nucleosome structure, which is the basic unit for compacting DNA. She led an extraordinary scientific breakthrough that effectively solved the three-dimensional structure of the nucleosome. This work is now cited in nearly every modern textbook of biochemistry and molecular biology.