As researchers have uncovered more and more of these "epigenetic" tags, they have begun to wonder how they are all connected. Now, research from the University of North Carolina School of Medicine has established the first link between the two most fundamental epigenetic tags -- histone modification and DNA methylation -- in humans.
Mouse embryonic stem cells (blue, green) lose DNA methylation (red) in the absence of UHRF1.
Credit: Strahl Lab, UNC School of Medicine
The study, which was published Sept. 30, 2012 by the journal Nature Structural & Molecular Biology, implicates a protein called UHRF1 in the maintenance of these epigenetic tags. Because the protein has been found to be defective in cancer, the finding could help scientists understand not only how microscopic chemical changes can ultimately affect the epigenetic landscape but also give clues to the underlying causes of disease and cancer.
"There's always been the suspicion that regions marked by DNA methylation might be connected to other epigenetic tags like histone modifications, and that has even been shown to be true in model organisms like fungus and plants," said senior study author Brian Strahl, PhD, associate professor of biochemistry and biophysics in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center. "But no one has been able to make that leap in human cells. It's been controversial in terms of whether or not there's really a connection. We have shown there is."
Strahl, along with his postdoctoral fellow Scott Rothbart, honed in on this discovery by using a highly sophisticated technique developed in his lab known as next generation peptide arrays. First the Strahl lab generated specific types of histone modifications and dotted them on tiny glass slides called "arrays." They then used these "arrays" to see how histone modifications affected the docking of different proteins. One protein – UHRF1 – stood out because it bound a specific histone modification (lysine 9 methylation on histone H3) in cases where others could not.
Strahl and his colleagues focused the rest of their experiments on understanding the role of UHRF1 binding to this histone modification. They found that while other proteins that dock on this epigenetic tag are ejected during a specific phase of the cell cycle, mitosis, UHRF1 sticks around. Importantly, the protein's association with histones throughout the cell cycle appears to be critical to maintaining another epigenetic tag called DNA methylation. The result was surprising because researchers had previously believed that the maintenance of DNA methylation occurred exclusively during a single step of the cell cycle called DNA replication.
"This role of UHRF1 outside of DNA replication is certainly unexpected, but I think it is just another way of making sure we don't lose information about our epigenetic landscape," said Strahl.
The research was funded by the National Institutes of Health and the North Carolina Biotechnology Center.
Study co-authors from UNC were Scott B. Rothbart, PhD, a postdoc in Strahl's lab at UNC; Krzysztof Krajewski, PhD, research assistant professor; and Jorge Y. Martinez, a former student in Strahl's lab.
Tom Hughes | EurekAlert!
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).
The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
16.08.2017 | Physics and Astronomy
16.08.2017 | Materials Sciences
16.08.2017 | Interdisciplinary Research