This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A protein that's essential to every cell's ability to turn off unnecessary genes is well known for its key function of compacting genes and its connection to cancer when it undergoes mutation. But until now, scientists weren't quite sure how the protein gets where it needs to go to keep genes bound up so they aren't activated.
In a new study, researchers found that this protein, called linker histone H1, initially flits around inside a cell with no clear aim even in the presence of its target: a nucleosome containing spooled-up segments of DNA. H1 binds directly to two DNA strands sticking out from the nucleosome but struggles to bind to the nucleosome itself until a chaperone protein escorts it there. The team used single-molecule experiments to visualize individual H1 proteins and their nucleosome targets before, during and after H1 bound to the DNA and to the center of the nucleosome.
Single-molecule methods provide a direct understanding of the target processes by quantifying molecular motions and interactions one molecule at a time, said senior author Michael Poirier, professor of physics at The Ohio State University. "Many proteins are dynamic, and the way you get at mechanistic dynamic information is by doing these single-molecule studies where you literally can watch in real time what individual molecules are doing," Poirier said. These insights are especially important when studying a protein with so much influence over cellular functions, he said.
"H1 is a key regulator of which genes are being used by a cell and which genes are not. If you want to understand how disease develops because gene expression is no longer working properly, then you need to understand how H1 works. Once you understand this, then you open up the possibility for new therapies that counteract this cause of disease." First author Ehsan Akbari, a research scientist in Poirier's lab, led the team's work.
The research was published Sept. 22 in Molecular Cell. Every cell in a plant, animal or human contains the organism's entire DNA. In human cells, our genome, which is 6 feet (1.8 meters) long, must fit inside the nucleus, which is less than one-tenth the width of a human hair.
To do this, sections of genomic DNA spool around a collection of histone proteins to form nucleosomes—similarly to how a watering hose might be organized in a backyard. Nucleosomes then fold in on each other, clumping together to form chromatin. The linker histone H1's job is to facilitate chromatin compaction, ensuring DNA segments containing genes the cell isn't using stay wrapped up and unavailable for expression.
Extract — continue reading at the source.
