November 22, 2012
Epigenetics Provides A Better Understanding Of The Inner Workings Of Our Brain
April Flowers for redOrbit.com - Your Universe Online
Hundreds of small regions of the genome that appear to be uniquely regulated in human neurons have been identified in a new study led by the University of Massachusetts. Humans are distinguished from other primates, such as monkeys and apes, by these regulatory differences. These features, which are neurons at the core of our cognitive abilities, may ultimately hold the key to our intellectual prowess. They might also be key to our potential vulnerability to a wide range of 'human-specific' diseases from Autism to Alzheimer's.
Primate genomes comprise billions of base pairs, and comparing only human and chimpanzee genomes alone have revealed close to 40 million differences, making an exploration of which features in the genome separate human neurons from non-human counterparts challenging to say the least. Most of these differences are thought to represent random "genetic drift" during evolution. The challenge became one of identifying the small set of changes that have functional consequences, as these might help to explain the genomic basis of the emergence of human-specific neuronal function.
Dr. Schahram Akbarian, from the University of Massachusetts and the Mount Sinai School of Medicine, says the key to the new study was not to focus on the "letters" of the DNA code. Instead, the team focused on the "font" or "typeface." The DNA strands of the genome are wrapped in protein to make a chromatin fiber. The way they are wrapped, the "chromatin state," reflects the regulatory state of that region of the genome — whether or not a given gene is turned on or off. Biologists have named this field of study "epigenetics" — the study of the "epigenome."
The research team set out to isolate small snippets of chromatin fibers from the frontal cortex. This is the region of the brain involved in complex cognitive operations. They analyzed the snippets for the chemical signals, called histone methylation, that define the regulatory state — basically the on / off switch — of the chromatin. This analysis identified hundreds of regions throughout the genome which showed a markedly different chromatin structure in neurons from human children to adults, compared to chimpanzees and macaques.
Interesting new leads involving the evolution of the human brain are being provided by this treasure trove of short genomic regions. Some of the regions have remained the same during primate evolution, however, some more tantalizing ones have recently changed. These changed regions have a DNA sequence that is unique to humans and our close extinct relatives, the Neanderthals and the Denisovans.
Some of these regulatory DNA regions appear to physically interact with each other inside the cell nucleus, the study found. This physical interaction occurs despite the regions being separated by hundreds of thousands of base pairs on the linear genome. Scientists call this phenomenon "chromatin looping," and it is implicated in controlling the expression of neighboring genes, including several with a critical role for human brain development.
The findings of this study draw further attention to the role of epigenetics and the epigenome in our biology and our evolution.
Dr. Akbarian notes, "Much about human biology and disease cannot be deduced by simply sequencing the genome. Mapping the epigenome of neurons and other cells will help us to better understand the inner workings of our brain, and where we are coming from."
The findings of this study were published online in PLOS Biology.