Beyond the four-letter alphabet of the genome, a far richer code dictates when and where genes are transcribed. The epigenome—defined by an ever-expanding list of modifications to DNA and the proteins that interact with it—determines which genes are dialed up or down and gives each cell type its unique personality. Thickening an already dense plot, three recent papers suggest that the brain may have its own epigenetic lingo.

One, published in Neuron on June 17, described the epigenome of three different types of neuron from the mouse brain—one excitatory, and two inhibitory. Among a slew of other findings, the study reported that neurons harbor a striking degree of cytosine methylation beyond the well-known cytosine-guanine (CpG) sites. This novel modification more closely correlated with gene expression and with neuronal phenotype than did the more common CpG methylation.

To generate a more detailed epigenetic map of neurons in the mouse brain, the researchers employed a technique called INTACT (isolation of nuclei tagged in specific cell types) to study nuclei from three types of neuron (see image above). The technique, which uses antibodies to capture nuclei expressing a protein tag, had been established in a plant model, and later used in flies, worms, and frogs, but never in mammals. INTACT isolates nuclei from homogenized tissue that is first frozen intact. This eliminates the need to first separate or sort the different types of cells, which can damage and/or activate neurons and confound results. INTACT allows researchers to obtain enough genetic material from specific cell types to run methylation and other epigenetic analyses.

Source:  AlzResearch Forum


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