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Unique epigenomic code identified during human brain development

Marga Behrens, Eran Mukamel, Terry Sejnowski, Joseph Ecker

From left: Marga Behrens, Eran Mukamel, Terry Sejnowski, Joseph Ecker

The frontmost part of the brain, the frontal cortwx, plays a key role in our ability to think, decide and act. The brain accomplishes all of this through the interaction of special cells such as neurons and glia. We know that these cells have distinct functions, but what gives them their individual identities? The answer lies in how each cell expresses the information contained in its DNA.

Changes in the epigenome, including chemical modifications of DNA, can act as an extra layer of information in the genome and are thought to play a role in learning and memory, as well as age-related cognitive decline. In a recent study, a team led by Joseph R. Ecker and Terrence J. Sejnowski showed that the landscape of DNA methylation, a particular type of epigenomic modification, is highly dynamic in brain cells during the transition from birth to adulthood, helping to understand how information in the genomes of cells in the brain is controlled from fetal development to adulthood.

In the study, published in Science, the scientists found that the patterns of DNA methylation undergo widespread reconfiguration in the frontal cortex of mouse and human brains during a time of development when synapses are growing rapidly. They identified the exact sites of DNA methylation throughout the genome in brains from infants through adults and found that one form of DNA methylation is present in neurons and glia from birth. Strikingly, a second form of DNA methylation that is almost exclusive to neurons accumulates as the brain matures, becoming the dominant form of methylation in the genome of human neurons.

These results help explain how the intricate DNA landscape of brain cells develops during the key stages of childhood. They also provide the first comprehensive maps of how DNA methylation patterns change in the mouse and human brain during development, forming a critical foundation for exploring whether changes in methylation patterns may be linked to human diseases, including psychiatric disorders.