July 5, 2013
Brain Epigenome Continues To Change Through Developmental Years
Brett Smith for redOrbit.com - Your Universe Online
While the entire genome has been sequenced and the codes of many genes have been identified, there are is a wide range of unknown mechanisms that interact with the code without changing "letters" of the DNA. These chemical changes to DNA are referred to as the epigenome, and a new study in the journal Science has revealed significant epigenomic activity during brain development.
DNA includes four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). An epigenomic process known as DNA methylation usually occurs where a cytosine base sits next to a guanine base in the DNA chain, known as CpG sites.
Previous research has shown in human embryonic stem cells and certain types of stem cells, DNA methylation also occurs when G does not follow C, a phenomenon called "non-CG methylation." This type of methylation was thought to disappear when stem cells later differentiate into specific body cells. However, the new study showed non-CG methylation appears in the brain's neurons long after stem cell differentiation, usually during childhood and adolescence when the brain is developing.
The scientists reached their findings by sequencing the genomes of mouse and human brain tissue, including neurons and glial cells taken during various life stages.
"This shows that the period during which the neural circuits of the brain mature is accompanied by a parallel process of large-scale reconfiguration of the neural epigenome," said co-author Joseph R. Ecker, professor and director of Salk Institute's Genomic Analysis Laboratory.
"The human brain has been called the most complex system that we know of in the universe," said co-author Ryan Lister, who worked in Ecker's laboratory at Salk and is now a group leader at The University of Western Australia. "So perhaps we shouldn't be so surprised that this complexity extends to the level of the brain epigenome.
"These unique features of DNA methylation that emerge during critical phases of brain development suggest the presence of previously unrecognized regulatory processes that may be critically involved in normal brain function and brain disorders."
The researchers said the construction of networks within the brain requires a long maturation process in which brain cells need to tweak the way they express their genetic code.
"DNA methylation fulfills this role," said study co-author Terrence J. Sejnowski, head of Salk's Computational Neurobiology Laboratory. "We found that patterns of methylation are dynamic during brain development, in particular for non-CG methylation during early childhood and adolescence, which changes the way that we think about normal brain function and dysfunction."
The team noted their study could form a critical foundation for exploring how methylation patterns may be linked to psychiatric disorders or other diseases. Some recent studies have shown DNA methylation playing a role in schizophrenia, depression, suicide and bipolar disorder.
"Our work will let us begin to ask more detailed questions about how changes in the epigenome sculpt the complex identities of brain cells through life," said co-author Eran Mukamel, from Salk's Computational Neurobiology Laboratory.
The study researchers said their future work will focus on determining whether minor alterations in the DNA methylation process could be associated to neurodevelopmental disorders.