Human Brain DNA Methylation in Evolution and Disease
Speaker
Prof. Soojin YiLocation
BioE 1001Info
DNA methylation is a critical regulatory mechanism underlying human brain development, learning, memory, and disease. In particular, the importance of cell-type specific epigenetic variation of non-coding regions in neuropsychiatric disorders, which are considered human-specific, is increasingly appreciated. We investigated evolutionary
dynamics of neuron and oligodendrocytes specific DNA methylation maps from human and non-human primate brains. The methylomes of the two cell-types are highly distinct. We found that the majority of cell-type epigenetic specificity has evolved before the split of humans and Catarrhine monkeys. The human brain has experienced remarkable changes of DNA methylation at both CpG and CpH contexts, with consequences on gene expression and cell type identities. Analyses of GWAS variants associated with neuropsychiatric disorders indicate that even though the majority of disease heritability is shared between human and Catarrhine monkeys, human-specific
differentially methylated regions harbor significant signals of genetic heritability for schizophrenia. These results provide insights into understanding the reprogramming of
cellular regulatory landscape and the genetic basis for the vulnerability to neuropsychiatric diseases.
