Forum for Science, Industry and Business

Work with Fungus Uncovering Keys to DNA Methylation

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.

Source: Eric Selker, professor of biology, 541-346-5197, selker@uoregon.edu

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
Further information:
http://www.uoregon.edu

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...