Rockefeller University researchers suggest that developing neurons don't just need the right genes to guide them as they grow, they need access to the right genes at the right times. A new study conducted on mice has shed light on the cause of mental retardation.
The improper functioning of one specific protein complex that normally suppresses gene activation has been found to be responsible for a mental retardation-like syndrome in mice.
It may even play a role in promoting susceptibility to drug addiction in humans.
"Our findings may facilitate the identification of mechanisms responsible for long term storage of environmental information in neurons as well as other cell types," said senior co-author Alexander Tarakhovsk, Irene Diamond Professor and head of the Laboratory of Lymphocyte Signaling.
"We now have an animal system which not only reproduces the human disease, but may also enable us to understand the underlying mechanisms," he added.
Although genes provide the fixed template that instructs our cells how to grow, increasing evidence suggests that gene activity is governed by a group of proteins known as histones. Histones are subjected to chemical modifications that can permit or prevent genes from becoming active.
During the past two decades, research by Rockefeller University's David Allis suggested that histone modification could generate a unique epigenetic "code" that regulates the specific recruitment of gene expression activators and repressors to individual genes.
The research program of the Greengard and Tarakhovsky labs focuses on GLP/G9a, an enzyme pair responsible for inducing an epigenetic mark widely known to silence gene expression in mammals, including humans.
By attaching two methyl chemical groups to a specific amino acid on a specific histone, GLP/G9a suppresses gene activity. Tarakhovsky and his colleagues, who study GLP/G9a and its role in epigenetic regulation of inflammatory responses, created a strain of mice that enables conditional removal of this complex in various cell types, including neurons in the adult brain.
The mice were subjected to a battery of behavioral tests and determined that they behave much like humans with a mental retardation syndrome.
The new findings are published in journal Neuron and journal Science.