Brain Function

Genetic Mapping of DNA Methylation Regulators in Human Cerebellum
2008 Seed Grant
Chunyu Liu, Ph.D.
University of Chicago

We were taught that changes in genes take place over many generations and through years of
natural selection. Would you be surprised to learn that our environment and the choices we
make in life today can influence our genetic code and have a profound effect on our health and
the health of our children in the near future?

The field of epigenetics is illustrating how quickly functions of one’s genetic code can be altered
through environmental changes. Epigenetics refers to changes in gene expression or phenotype
(appearance) that do not change the underlying deoxyribonucleic acid (DNA; the chemical
substance of genes) sequence. In recent years, researchers have identified various chemical
modifications to DNA and to histones (proteins that associate tightly with DNA) that can
determine when or even if a given gene is expressed.

Dr. Chunyu Liu studies one of those chemical modifications – DNA methylation. DNA
methylation involves the addition of a methyl group to DNA and is essential for normal
development and cellular differentiation in higher organisms. DNA methylation can be altered by
environment. More specifically, it can be altered by factors like diet, radiation and drugs.
Abnormal DNA methylation has been associated with diseases such as cancer and diabetes as
well as multiple sclerosis, schizophrenia and other neuropsychiatric disorders. Studies have
suggested that DNA methylation could be a heritable quantitative trait. However, the regulation
mechanism of DNA methylation of specific genes, especially in the brain, is still largely a
mystery. Like all other quantitative traits, genetic regulation factors that affect traits can be
mapped by genetic methods. Dr. Liu uses genetic methods to map regulatory elements of DNA
methylation in the human brain.

Liu’s lab compared brain samples from people afflicted with schizophrenia, bipolar disorder,
major depression, and healthy controls. With the funding from a BRF Seed Grant, Liu’s lab
became the first group to identify that both regional and distant genomic variations could affect
the methylation level of a specific DNA sequence in the brain. The study showed a convincing
evidence of genetic factors of epigenetic traits. Environmental factors and genetic factors
underlying human phenotypes and diseases found their shared spaces. Now, Liu is working on
a study that will investigate DNA methylation and gene expression differences among the same
groups— individuals with schizophrenia, bipolar disorder, major depression and healthy
controls. The results of these studies will help scientists better understand the mechanisms of
DNA methylation and regulation of gene expression as well as the biological basis of disease,
particularly neuropsychiatric diseases.

According to the World Health Organization, as many as 450 million people worldwide suffer
from a mental or behavioral disorder.

Dr. Chunyu Liu, Psychiatry and Behavioral Neuroscience at the University of Chicago, is
working to make a difference in the lives of so many by determining the link between genetic
factors, environmental factors and neuropsychiatric diseases.

Dr. Liu was awarded a BRF Seed Grant in 2008. To date, the data from this grant has
generated nine research articles in important scientific journals such as American Journal of
Human Genetics, Molecular Psychiatry and Schizophrenia Research.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The role of microglial lysosomes in selective neuronal vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the nervous system constructs internal models of the external world
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the orchestra of movement—functional role of striatal astrocytes in health and disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…