Whoever claims cartography is a lost art hasn’t visited the Salk Institute lately. The cliffside research palace in La Jolla is home to a number of ambitious researchers who’ve been busy the last few years mapping every nook and cranny of the epigenome. Most recently, a team of clever researchers led the charge on mapping “genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan.”
Here’s what they found:
- The methylome undergoes widespread reconfiguration throughout neurodevelopment that occurs from the fetal to young adult stage.
- These changes were in tempo with synaptogenesis, a process involved in forming the connections (synapses) that allow our brain cells to communicate.
- “The relationship between [CpG] methylation patterns and the function of neuron- or astrocyte [the brains ‘helper’ cells]-specific gene sets suggests a role for DNA methylation in distinguishing these two broad classes of cortical cells”
- Surprisingly, non-CpG DNA methylation builds up neurons, but not glia (like astrocytes) to become the dominant form of methylation in our brain’s genome.
- There’s a unique non-CpG methylation signature on genes that escape X-chromosome inactivation.
- And as if all this wasn’t enough, they also decided to generate some single-base resolution 5hmc maps. These showed that 5hmc marks regulatory regions in the developing fetal brain genome that are to then be CpG demethylated by Tet2 and activated in the adult brain. Ultimately this suggests that there is “a hydroxymethylation signature of developmentally activated regions.”
“The human brain has been called the most complex system that we know of in the universe,” says first author Ryan Lister. “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.”
“These conclusions obtained from our genome-wide, base-resolution, cell-type specific DNA methylomes for brain cells through key stages of development are the first steps toward unraveling the genetic program and experience-dependent epigenetic modifications leading to a fully differentiated nervous system.”