Featured Research

from universities, journals, and other organizations

Permanent changes in brain genes may not be so permanent after all

Date:
January 27, 2014
Source:
Johns Hopkins Medicine
Summary:
In normal development, all cells turn off genes they don’t need, often by attaching a chemical methyl group to the DNA, a process called methylation. 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.

In normal development, all cells turn off genes they don’t need, often by attaching a chemical methyl group to the DNA, a process called methylation. 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.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Junjie U Guo, Yijing Su, Joo Heon Shin, Jaehoon Shin, Hongda Li, Bin Xie, Chun Zhong, Shaohui Hu, Thuc Le, Guoping Fan, Heng Zhu, Qiang Chang, Yuan Gao, Guo-li Ming, Hongjun Song. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience, 2013; DOI: 10.1038/nn.3607

Cite This Page:

Johns Hopkins Medicine. "Permanent changes in brain genes may not be so permanent after all." ScienceDaily. ScienceDaily, 27 January 2014. <www.sciencedaily.com/releases/2014/01/140127141555.htm>.
Johns Hopkins Medicine. (2014, January 27). Permanent changes in brain genes may not be so permanent after all. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2014/01/140127141555.htm
Johns Hopkins Medicine. "Permanent changes in brain genes may not be so permanent after all." ScienceDaily. www.sciencedaily.com/releases/2014/01/140127141555.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins