ACS Meeting News: Method watches nucleosomes open and close

It takes a lot of packaging to squeeze DNA into the nucleus of a cell. The DNA in our chromosomes is packaged into nucleosomes, which consist of about 150 DNA base pairs wrapped around eight-protein spools called histones.

“The level of gene packaging in a human nucleus is extreme,” said Tae-Hee Lee, a chemistry professor at Pennsylvania State University. “Two meters of DNA is packaged into a 10-µm nucleus. That’s the equivalent of about 30 miles of string compacted in a basketball.”

Copying or reading the DNA requires getting through all that packaging. Researchers have hypothesized that a path to the DNA opens up during thermally activated spontaneous motions of the histones and DNA. In a session sponsored by the Division of Analytical Chemistry at the ACS national meeting in Philadelphia, Lee described work demonstrating that such motions really do happen. The work also was published earlier this month (J. Phys. Chem. B 2016, DOI:10.1021/acs.jpcb.6b06235).

Lee’s group immobilized nucleosomes on a microscope slide and monitored the complexes using a method based on fluorescence resonance energy transfer (FRET).

Through a combination of two techniques, the team analyzed the FRET signals to quantify the motions of the histone proteins in the nucleosomes. They found that a protein dimer dissociates from the histone core every three milliseconds and moves back into place within two milliseconds. Modifications of the histone, including acetylation at a particular amino acid, affect these dynamics without significantly altering the histone structure.

“It is quite exciting to see these more extensive single-molecule studies on nucleosome dynamics,” said Peter G. Wolynes, a chemistry professor at Rice University, who uses computational methods to study nucleosomes. “The system is central to understanding gene regulation, and its large number of components have made ensemble studies complex. The single-molecule approach allows much greater clarity.”

Vasily M. Studitsky, an expert on epigenetics and gene regulation at Fox Chase Cancer Center in Philadelphia, told C&EN: “Although the majority of past studies in the field of epigenetics were focused on nucleosome structure, it seems very likely that future analysis of chromatin dynamics will help to reveal new fascinating mechanisms that simply cannot be detected by current, mostly structure-oriented, technologies.”

RELATED: Putting DNA in a Bind