Seminar

Evolution of Human Brain and Neuropsychiatric Disorders through the Lens of Cell-Type Specific Epigenetic Marks

Soojin Yi

DNA methylation and other epigenetic modifications play critical regulatory roles in 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. In this talk, I will discuss my efforts to understand impacts of epigenetic changes on brain evolution and neuropsychiatric disorders, by investigating these marks from human and non-human primate brains. We have demonstrated that whole genome methylomes of two major cell types in the brain are highly distinct and 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. Data on gene expression and chromatin accessibility at single nuclei resolution further demonstrate cellular regulatory changes at multiple levels during the evolution of human brains. These results advance our understanding of the reprogramming of cellular regulatory landscape and the genetic basis for the vulnerability to neuropsychiatric diseases.