Study illuminates roles of novel epigenetic chemical in the brain

September 17, 2012, Centre for Addiction and Mental Health

Researchers from the Centre for Addiction and Mental Health (CAMH) have identified a new role of a chemical involved in controlling the genes underlying memory and learning.

"The brain is a tissue, and we know that require various genes to be expressed," says CAMH Senior Scientist Dr. Art Petronis, who is a senior author on the new study. "Our research has identified how the chemical 5-hmC may be involved in the epigenetic processes allowing this plasticity." Dr. Petronis is head of the Krembil Family Epigenetics Laboratory in CAMH's Campbell Family Mental Health Research Institute.

5-hmC is an epigenetic modification of DNA, and was discovered in humans and mice in 2009. DNA modifications are to DNA. They flag genes to be turned "on" – signalling the genome to make a protein – or turned "off." As the overwhelming majority of cells in an individual contain the same , this pattern of flags is what allows a neuron to use the same genome as a blood or , but create a completely different and specialized .

The research, published online in Nature Structural & Molecular Biology, sheds light on the role of 5-hmC. Intriguingly, it is more abundant in the brain than in other tissues in the body, for reasons not clear to date.

The CAMH team of scientists examined DNA from a variety of tissues, including the mouse and human brain, and looked at where 5-hmC was found in the genome. They detected that 5-hmC had a unique distribution in the brain: it was highly enriched in genes related to the synapse, the dynamic tips of brain cells. Growth and change in the synapse allow different brain cells to "wire" together, which enables learning and memory.

"This enrichment of 5-hmC in synapse-related genes suggests a role for this epigenetic modification in learning and memory," says Dr. Petronis.

The team further showed that 5-hmC had a special distribution even within the gene. The code for one gene can be edited and "spliced" to create several different proteins. Dr. Petronis found that 5-hmC is located at "splice junctions," the points where the gene is cut before splicing.

"5-hmC may signal the cell's splicing machinery to generate the diverse proteins that, in turn, give rise to the unprecedented complexity of the brain," he says.

The research team is continuing to investigate the role of 5-hmC in more detail, and to determine whether 5-hmC function is different in people with bipolar disorder and schizophrenia compared to people without these diagnoses.

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JVK
1 / 5 (1) Sep 18, 2012
The epigenetic effects of nutrient chemicals and pheromones on intracellular signaling and stochastic gene expression could create a pattern responsible for cell memory of what to eat, which controls reproduction and adaptive evolution via ecological, social, neurogenic, and socio-cognitive niche construction. Is there another model for that? I think that looking at the role of epigenetic chemicals in the brain with a one by one approach is not very cost effective.
JVK
1 / 5 (1) Sep 18, 2012
"...5hmC modifications are quite dynamic; some change during maturation, and some change during the aging process," says senior author Peng Jin, associate professor of human genetics at Emory University School of Medicine. "Based on those alterations, our thought, right now, is that it seems like this 5hmC may represent another layer of gene regulation rather than simply the byproduct of demethylation."

http://www.biotec...471.html

The epigenetic effects of nutrient chemicals and pheromones on gonadotropin releasing hormone, maturation of the brain, and synaptic plasticity linked changes during the aging process also links the sensory environment to 5-hmC and chemical control of genes underlying memory and learning.

Kohl, J.V. (2012) Human pheromones and food odors: epigenetic influences... Socioaffective Neuroscience & Psychology, 2: 17338. http://dx.doi.org...i0.17338

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