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
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences