Historically, scientists believed methyl groups could only stick to a particular DNA sequence: a cytosine followed by a guanine, called CpG. But in recent years, they have been found on other sequences, and so-called non-CpG methylation has been found in stem cells, and in neurons in the brain.
Now, a team of researchers at Johns Hopkins has discovered that non-CpG methylation occurs later and more dynamically in neurons than previously appreciated, and that it acts as a system of gene regulation, which can be independent of traditional CpG methylation.
In a study described in the January 28 issue of Nature Neuroscience, the Hopkins team describes this new gene control mechanism and how it may contribute to Rett Syndrome, a nervous system disorder affecting mostly girls that causes problems with movement and communication.
The team, led by Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine's Institute for Cell Engineering's Stem Cell Program, had found non-CpG methylation prevalent in neurons, a finding that surprised them, since this wasn’t found in any other cells besides stem cells.
By looking at what genes were being transcribed in neurons, he and his colleagues found that, like the form of methylation scientists had seen in stem cells, non-CpG methylation stops genes from being expressed. They also mapped the genome to find where non-CpG methylation happens, and found that it carves out its own niche, and are distributed in regions without CpG methlyation. "That was the first hint that maybe it can function independently of CpG methylation," Song says.
The new kind of methylation also seems to operate under different rules. Scientists have long thought methylation was final. Once a cytosine gets a methyl stuck to it, so the story went, that gene is shut off forever. "This became dogma," Song says. "Once cells become the right type, they don't change their identity or DNA methylation."
But non-CpG methylation seems to happen later, when the neuron is mature—and even after conventional wisdom said it was irreversible. The researchers learned this from an experiment in which they knocked out in adult mice the enzymes that attach methyl groups to DNA. They found the neurons still had just as much CpG methylation, but the non-CpG methylation dropped off. This suggests that non-CpG methylation is an active process, Song says, with methyl groups continually being taken off and put back on, adding to evidence that non-CpG methylation may play more of a role in managing operations in mature cells.
The researchers also found a way that non-CpG methylation is similar to CpG methylation in one important way: it's read by MeCP2, an enzyme long identified as a player in methylation.
That's significant because a mutation in MeCP2 causes Rett Syndrome, and understanding DNA methylation is key to understanding this syndrome. The disorder occurs, Song says, when working copies of the gene for MeCP2 are silenced during development.
Other authors on the paper include Junjie Guo, Yijing Su, Joo Heon Shin, Jaehoon Shin, Bin Xie, Chun Zhong, Shaohui Hu, Heng Zhu, Yuan Gao and Guo-li Ming, all of Johns Hopkins University;Hongda Li and Qiang Chang of the University of Wisconsin-Madison; and Thuc Le and Guoping Fan of University of California Los Angeles.
This research was supported by the National Institute of Neurological Disorders and Stroke(NS047344, NS048271 and NS072924), National Institute of Environmental Health Sciences (ES021957), the National Institute of Mental Health (MH087874), National Institute of Child Health and Human Development (HD06918, HD064743 and HD066560), the Simons Foundation Autism Research Initiative, NARSAD, the Maryland Stem Cell Research Fund (MSCRF) and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.
Nature Neuroscience articleContact Information
Vanessa McMains | Newswise
Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences