Proper DNA methylation is required for normal development, gene function and overall genome stability, and disruption of methylation has long been linked to cancer and brain diseases.

“Because disruption in DNA methylation causes Rett syndrome, which leads to severe mental retardation and motor dysfunction, we suspected that methylation itself might be important in normal brain development,” says James Potash, M.D., M.P.H, associate professor of psychiatry at Hopkins.

The group then began cataloging the methylation sites on or around genes taken from the cerebral cortex, integral to higher thought processes; the cerebellum, central to motor control; and the pons, which acts as a relay station in the brain stem. These brain regions are widely different in their location and makeup. They compared DNA from different parts of each brain sample using a gene chip that tested more than 1,500 sites in the genome to determine which were methylated.

“What we found were striking differences in DNA methylation depending on where we looked,” says Feinberg.

Specific patterns of methylation were related to brain region and were unrelated to age, gender or cause of death.

“What's really interesting about this work is that epigenetics probably helps control the development of one cell type from another,” says Potash. “This study raises the possibility that errors in development might underlie brain diseases such as bipolar disorder, autism, major depression and schizophrenia.”

The research was funded by the National Institutes of Health.

Authors on the paper are Christine Ladd-Acosta, Sarven Sabunciyan, Robert Yolken, Tiffany Dinkins, Pauline Callinan, Potash and Feinberg, all of Hopkins; Jonathan Pevsner of the Kennedy-Krieger Institute, Baltimore; Maree Webster of Uniformed Services University of the Health Sciences, Bethesda, Md.; and Jian-Bing Fan of Illumina, San Diego, Calif.

On the Web:
http://www.hopkinsmedicine.org/ibbs/research/epigenetics/
http://www.ajhg.org