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
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
The research was funded by the National Institutes of
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.