Hopkins Study Suggests Non-CpG Methylation Is Reversible System of Gene Regulation That May Contribute to Rett Syndrome

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, methyl groups 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 that was published online on December 23, 2013 in 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 research 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 the team, because this wasn't found in any other cells other than 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 the sites are distributed in regions without CpG methlyation. "That was the first hint that maybe it can function independently of CpG methylation," Dr. Song says.
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