Nav: Home

The nanoscopic structure that locks up our genes

January 11, 2018

Wireless headphones, two yo-yos connected by a string, earmuffs: all these items could be used to describe a tiny structure inside a cell's nucleus. For decades, scientists could only speculate about the shape of heterochromatin, a type of chromatin--which consists of tightly packed DNA and proteins. Recently, however, researchers from the Okinawa Institute of Science and Technology, Graduate University (OIST) and Waseda University have been able to define its structure thanks to new, high-contrast imaging in cryo-electron microscopy. Their work appears this January in the journal Molecular Cell.

The new research shows that, although tightly packed, heterochromatin is perhaps less dense than previously thought. Made up of nucleosomes--roll-shaped bundles of DNA and protein--the heterochromatin is connected by a velcro-like feature called "Heterochromatin Protein 1 (HP1)." This fundamental feature allows the body to "lock down" genes so they cannot be transcribed.

"Life as we know it relies on these principles," said Matthias Wolf, one of the leading authors of the paper and head of the Molecular Cryo-Electron Microscopy Unit at the Okinawa Institute of Science and Technology, Graduate University (OIST).

"This work is an example of a very fruitful collaboration, which would not have been possible by any of the research groups alone," said Hitoshi Kurumizaka, the leading author of the study at Waseda University. There, along with Shinichi Machida, an assistant professor at Waseda and co-first author on the paper, researchers successfully purified heterochromatin in vitro. Researchers at OIST imaged these samples in glass-like amorphous ice, which contains hundreds of pieces of heterochromatin, under a cryo-electron microscope.

Using a computer algorithm to classify individual particles by type, the scientists "cut out" those particles facing in the same direction. Then, they stacked these digital cutouts atop one another, combining hundreds of images to create a clearer picture. Wolf demonstrated the concept by placing his hands atop each other.

"If everything fits perfectly then the thumbs and all the fingers align," he said, "and you get higher resolution."

Based on these images, Wolf and his colleagues created three-dimensional reconstructions of the heterochromatin. Because of the structure's flexibility, it was difficult to get a precise idea of its shape, said Yoshimasa Takizawa, group leader of the unit and co-first author on the paper. Takizawa collected hundreds of thousands of images of individual particles to obtain better resolution.

"We were surprised at how it looked," he said of the heterochromatin's shape, "but this could be consistent with other functions, like the binding of other proteins to exposed DNA."

In the future, the researchers hope to use their knowledge to understand higher order structures, like entire strings of nucleosomes.
-end-


Okinawa Institute of Science and Technology (OIST) Graduate University

Related Heterochromatin Articles:

The nanoscopic structure that locks up our genes
For decades, scientists could only speculate about the shape of heterochromatin.
The isoforms of the HP1 protein regulate the organization and structure of heterochromatin
Researchers from the Epigenetics and Cancer Biology Program of the Bellvitge Biomedical Research Institute (IDIBELL), led by Dr.
Penn study shows how female immune cells keep their second x chromosome shut off
In a new study, a team from the University of Pennsylvania describes how X chromosome inactivation is regulated in the immune system's B cells as they develop in bone marrow and when they encounter antigens.
A molecular garbage disposal complex has a role in packing the genome
New research from the Korea Institute of Science and Technology, to be published in the Journal of Biological Chemistry on Oct.
Microscope invented at marine biological laboratory illuminates chromosomal 'dark matter'
Using a microscope invented at the Marine Biological Laboratory (MBL), a collaborative team of biologists, instrument developers, and computational scientists has for the first time measured the density of a relatively inscrutable, highly condensed form of chromosomal material (heterochromatin) that appears in the cells of human beings and other eukaryotes.
Histone 1, the guardian of genome stability
Genomic instability is the main risk factor for tumor development in humans.
Impaired DNA replication can cause epigenetic changes inherited for several generations
Scientists reveal that a fault in the process that copies DNA during cell division can cause epigenetic changes that may be inherited for up-to five generations.
Researchers find new mechanism for genome regulation
The mechanisms that separate mixtures of oil and water may also help the organization of a part of our DNA called heterochromatin, according to a new Berkeley Lab study.
Discovery of a novel chromosome segregation mechanism during cell division
When cells divide, chromosomes need to be evenly segregated. This equal distribution is important to accurately pass genetic information to the next generation.
Brian Luke awarded a Heisenberg Professorship
Brian Luke, a Group Leader at the Institute of Molecular Biology (IMB) in Mainz, has been awarded a prestigious Heisenberg Professorship from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).

Related Heterochromatin Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Setbacks
Failure can feel lonely and final. But can we learn from failure, even reframe it, to feel more like a temporary setback? This hour, TED speakers on changing a crushing defeat into a stepping stone. Guests include entrepreneur Leticia Gasca, psychology professor Alison Ledgerwood, astronomer Phil Plait, former professional athlete Charly Haversat, and UPS training manager Jon Bowers.
Now Playing: Science for the People

#524 The Human Network
What does a network of humans look like and how does it work? How does information spread? How do decisions and opinions spread? What gets distorted as it moves through the network and why? This week we dig into the ins and outs of human networks with Matthew Jackson, Professor of Economics at Stanford University and author of the book "The Human Network: How Your Social Position Determines Your Power, Beliefs, and Behaviours".