DNA methylation is essential for normal growth and development in plants and animals. It has been implicated in long-term memory, and irregularities in its process are associated with diseases such as cancer.
In the UO's Institute of Molecular Biology, Eric U. Selker and members of his laboratory use a quickly reproducing and easy-to-manipulate fungus, Neurospora crassa, to explore the control of DNA methylation. Neurospora is considered the simplest model organism for such research.
Reporting in the Dec. 15 issue of the journal Genes & Development, Selker and Keyur K. Adhvaryu, a postdoctoral researcher in the Selker lab, document that the enzyme protein phosphatase PP1 is necessary for normal methylation of DNA.
In the nucleus of eukaryotic cells, DNA is wrapped around histone proteins to form chromatin, and one histone, H3, turns out to be critical for DNA methylation. "It was long thought that histones were simply structural proteins, but we are learning that these proteins are also informational," Selker said.
This was demonstrated in the journal Nature in 2001 by Selker and his former postdoctoral research associate Hisashi Tamaru. They found that a protein required for DNA methylation, DIM-5, is an enzyme that adds a methyl group onto lysine 9 of histone H3. "This was the first solid indication that chromatin is important for DNA methylation," Selker said.
The new paper by Adhvaryu and Selker shows that PP1 is important to remove phosphates attached to serine 10 of H3, the site immediately adjacent to the site that DIM-5 needs to methylate, leading to DNA methylation.
In an accompanying article in the same issue of Genes & Development, Wolfgang Fischle, a biochemist at the Max-Planck Institute for Biophysical Chemistry, praises the findings of Selker and Adhvaryu. He writes that there appears to be extensive "crosstalk" involved in the chemical modifications that occur on histones to influence other enzymes that interact with chromatin "Adhvaryu and Selker provide novel insights into an intricate regulatory network involving histone phosphorylation, histone methylation and DNA methylation," he noted.
"DNA methylation seems to be a luxury item in Neurospora, which means we can manipulate it as we wish, making mutants that don't do it and thereby identify important players," Selker said. "We are identifying how DNA methylation is controlled and what it does in this organism. Our assumption is that a lot of what we find in Neurospora will be applicable to other systems."
In this case, Selker said, Keyur demonstrated very nicely, in a couple different ways, that protein phosphatase PP1 is required for normal DNA methylation. "DNA methylation is involved in a silencing of invasive DNA as well as a variety of normal genes, including those on the inactive X chromosome, those subjected to imprinting, and well as tumor suppressor genes," he said, adding that methylation of the latter class of genes can lead to cancer.
The research was funded by a grant from the National Institutes of Health to Selker and in part by an American Heart Association fellowship to Adhvaryu.About the University of Oregon
Source: Eric Selker, professor of biology, 541-346-5197, email@example.com
Links: Selker faculty Web page: http://www.molbio.uoregon.edu/facres/selker.php; UO department of biology: http://biology.uoregon.edu/people/faculty.php
Jim Barlow | Newswise Science News
'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology
Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University
Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Life Sciences
23.10.2017 | Physics and Astronomy
23.10.2017 | Health and Medicine