Our brains might not recall our early years, but increasing evidence supports that our methylomes just might. A few studies have shown that cuddles from mama rats—or a lack thereof—are known to affect their offspring’s long-term health and behavior by changing the brain’s DNA methylation patterns over a large scale.
Now, a Canadian research effort led by Matthew Suderman, Patrick McGowan, and Aya Sasaki has demonstrated that humans too present similar large-scale DNA methylation patterns. This suggests that DNA methylation patterning resulting from early life experiences is evolutionarily conserved.
Previous rat studies showed that a large swath of the genome around the NR3C1 locus, which houses the glucocorticoid receptor gene, has different DNA methylation patterns depending on if the animals received proper maternal care. The Canadians wanted to see if the same observation held true for humans.
The investigators compared hippocampal samples from deceased people who experienced childhood abuse and committed suicide and compared these with non-abused controls. By combining MeDIP with custom tiling microarrays, they analyzed the DNA methylation profiles over 6.5 million base pairs around NR3C1 locus. After comparing the human and rat profiles, they found that the hundreds of DNA methylation differences that:
- Were nonrandomly distributed.
- Clustered by genomic location. Some clusters were as large as 1 million bases.
- Appeared to target gene promoters and other regulatory regions.
The protocadherin genes particularly stuck out. These are known to be regulated by promoter methylation and are thought to participate in synaptic function and neuronal connectivity.
To get the details while they are still fresh, click over to this week’s issue of the PNAS, October (2012)