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The newspaper of The Johns Hopkins University December 10, 2007 | Vol. 37 No. 14
Epigenetic 'Marks' Might Account for Multiple Functions of the Brain

By Audrey Huang
Johns Hopkins Medicine

A team of Johns Hopkins scientists has cataloged chemical tags attached to more than 800 genes from 76 human brain samples and collected the first evidence of how these special, inherited epigenetic "marks" might account for different brain functions. The results appear in the December issue of The American Journal of Human Genetics.

"It's quite remarkable how clear the differences are, and a bit surprising because the genes we looked at weren't necessarily known to be brain function genes," said Andrew Feinberg, professor of medicine, oncology and molecular biology and genetics and director of the Center for Epigenetics at Johns Hopkins.

"It makes sense that different geographic regions of the brain, because they're responsible for a range of operations from memory to motor control, would be using different genes," he said, "but we think this is the first evidence that specific brain functions, carried out by specific genes, may be determined by their epigenetic signatures."

The signatures at play are known as methyl groups (particular combinations of a carbon and three hydrogen molecules), which can attach directly to the basic component of all genes, DNA.

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.

James Potash, associate professor of psychiatry at Johns Hopkins, said, "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."

The group catalogued 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. The researchers 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 they found, Feinberg said, was "striking differences in DNA methylation depending on where we looked."

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

Potash said that "what's really interesting about this work is that epigenetics probably helps control the development of one cell type from another. 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 Johns Hopkins; Jonathan Pevsner, of the Kennedy- Krieger Institute; Maree Webster, of Uniformed Services University of the Health Sciences, Bethesda, Md.; and Jian-Bing Fan of Illumina, San Diego.


Related Web sites

Epigenetics Center at Johns Hopkins
'The American Journal of Human Genetics'


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