DNA methylation is a process, in normal development, whereby cells turn off genes they don’t need by attaching a chemical methyl group to the DNA. 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, methylation has been found on other DNA sequences in stem cells and in neurons. This has become known as non-CpG methylation.

In a paper published in the January 28th issue of the journal Nature Neuroscience, a research team led by 2008 NARSAD Independent Investigator Grantee Hongjun Song, Ph.D., Professor of Neurology and Director of Johns Hopkins Medicine’s Institute for Cell Engineering’s Stem Cell Program demonstrates that this non-CpG methylation occurs later and more dynamically in neurons than previously thought, and that it acts as a system of gene regulation, which can be independent of traditional CpG methylation. Their work also shows that DNA methylation is not necessarily final―the gene is not necessarily turned off forever.

"This became dogma," explains Dr. Song. "Once cells become the right type, they don't change their identity or DNA methylation." But in this new work, it looks like non-CpG methylation happens later, when the neuron is mature. This suggests that non-CpG methylation is an active process, Dr. 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: it's read by MeCP2, an enzyme long identified as a player in methylation. This may hold promise for improved treatments of Rett Syndrome, a nervous system disorder affecting mostly girls that causes problems with movement and communication. A mutation in MeCP2 is believed to cause Rett Syndrome, when working copies of the gene for MeCP2 are silenced during development.

The researchers from Johns Hopkins collaborated with neuroscientists from the University of Wisconsin-Madison and the University of California Los Angeles. Additional NARSAD Grantees included Guo-li Ming, M.D., Ph.D., of Johns Hopkins University and Qiang Chang, Ph.D., from the University of Wisconsin-Madison.

Read more about this research in the press release from Johns Hopkins Medicine.

Read an abstract of this research.