The team of scientists discovered a relationship between DNA methylation and the positioning of nucleosomes, which compact and regulate access to DNA in the nucleus of a cell. The discovery was made using high-throughput DNA sequencing to study the sites on DNA where high levels of methylation were occurring, said Matteo Pellegrini and Steve Jacobsen, researchers with the Broad Stem Cell Research Center at UCLA and senior co-authors of the study.
The study appeared Sun., May 30, 2010 in the early online edition of the peer-reviewed journal Nature.
The processes required for the survival of a cell depend on the cell's ability to store and read the genetic information encoded in its DNA. Packaging the long DNA into a tiny nucleus is complicated because the DNA still needs to be accessible to the cell's molecular machinery. The molecules that compact DNA are called the nucleosome core particles. Each one has about 147 base pairs of DNA wrapped around it. This interaction forms a sort of scaffolding for compaction of the long DNA polymer, while allowing it to be accessible for events such as methylation.
DNA methylation is important in regulating genes that play a role in the differentiation of embryonic stem cells and in the development of some cancers, Jacobsen said.
“Changes in DNA methylation are behind a lot of what makes a stem cell a stem cell. As the cell differentiates, the DNA methylation tends to change. One aspect of understanding methylation is understanding its pattern and how it’s laid out within the cell,” said Jacobsen, a professor of molecular, cell and developmental biology and a Howard Hughes Medical Institute investigator.
In this study, the UCLA team found that the DNA wrapped around nucleosomes is more highly methylated than flanking DNA, which links adjacent DNA/nucleosome complexes.
“These results indicate that nucleosome positioning influences DNA methylation patterning throughout the genome and that DNA methyltransfereases (the enzymes that methylate DNA) preferentially target nucloesome-bound DNA,” said Pellegrini, an associate professor of molecular, cell and developmental biology and an informatics expert.
The work was initially done in Arabidopsis, a mustard weed commonly used in plant research. Once the DNA methylation and nucleosome positioning patterns emerged, they repeated the work in human stem cells. Pellegrini and Jacobsen found similar patterns in the human stem cells.
One of the most important, unknown aspects of DNA methylation, Jacobsen said, is how the cell determines where the event occurs, and the pattern of nucleosome positions has emerged as an important determinant of methylation.
The findings could have implications in fighting cancer because DNA methylation patterns go awry in cancer, often causing tumor suppressor genes to switch off. The more scientists know about the cellular mechanisms that lay down the correct DNA methylation patterns, the more that process can be manipulated. In the future, this type of research may lead to techniques that result in the ability to control the patterns that go awry and lead to cancer, thus preventing a malignancy.
And because DNA methylation is important in stem cell differentiation, this knowledge could lead to ways to correct defects in stem cells lines in the future.
Funding for the two-year study came from the National Science Foundation, the Howard Hughes Medical Institute and the Broad Stem Cell Research Center at UCLA.
The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.
Kim Irwin | Newswise Science News
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences