Global Epigenomic Reconfiguration During Mammalian Brain Development
Map of methylation mirrors changes in brain development
Researchers have debuted the most comprehensive map to date showing how the suite of methyl tags on the DNA of brain cells changes across the genome over a lifetime1. The map, published 4 July in Science, suggests that shifting patterns of methylation may guide key periods of brain development.
“Non-CG methylation turns out to have a dramatic effect during human neuron development,” says Ecker. “We found that it was a major player in epigenetic modification.”
There is a rapid increase in non-CG methylation from birth to 2 years in people and the equivalent age range, 2 to 4 weeks, in mice — which coincides with the rapid formation of connections between neurons — the study found. This pattern of methylation remains consistent in both people and mice across many genes, hinting at its importance.
Global Epigenomic Reconfiguration During Mammalian Brain Development.
DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Finally, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain, and that CG demethylation at these hmC-poised loci depends on Tet2 activity.
Further Readings of Interest
Brain Transcriptional and Epigenetic Associations with Autism
Full article – link
We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling.
Brain Explosion – Just before Birth
Wiring the Brain, Through Experience
“ScienceDaily (June 6, 2012) — New research shows mice brains are ‘very wired up’ at birth, and suggests experience selects which connections to keep.
As reported on June 7 in the journal Neuron, a team of researchers led by Jeff Lichtman, the Jeremy R. Knowles Professor of Molecular and Cellular Biology, has found that just days before birth mice undergo an explosion of neuromuscular branching. At birth, the research showed, some muscle fibers are contacted by as many as 10 nerve cells. Within days, however, all but one of those connections had been pruned away.
“By the time mammals — and humans would certainly be included — are first coming into the world, when they can do almost nothing, the brain is probably very wired up,” Lichtman said. “Through experience, the brain works to select, out of this mass of possible circuits, a very small subset…and everything else that could have been there is gone.
“I don’t think anyone suspected that this was taking place — I certainly didn’t,” he continued. “In some simple muscles, every nerve cell branches out and contacts every muscle fiber. That is, the wiring diagram is as diffuse as possible. But by the end, only two weeks later, every muscle fiber is the lifelong partner of a single nerve cell, and 90 percent of the wires have disappeared.”
“In future studies, Lichtman plans to study how those decisions are made, work that could potentially lead to insight into a number of disorders, including autism.
“That is one theory people have talked about, whether autism could be a disorder where connections that should have been trimmed back weren’t, and as a result stimuli are much more intense than they should be,” he said. “There are stories about children with autism spectrum disorders who cannot run in their bare feet on grass, because it’s just too painful.”
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