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Evolution of DNA methylation in the human brain.

Nature communications (2021-04-03)
Hyeonsoo Jeong, Isabel Mendizabal, Stefano Berto, Paramita Chatterjee, Thomas Layman, Noriyoshi Usui, Kazuya Toriumi, Connor Douglas, Devika Singh, Iksoo Huh, Todd M Preuss, Genevieve Konopka, Soojin V Yi
ABSTRACT

DNA methylation is a critical regulatory mechanism implicated in development, learning, memory, and disease in the human brain. Here we have elucidated DNA methylation changes during recent human brain evolution. We demonstrate dynamic evolutionary trajectories of DNA methylation in cell-type and cytosine-context specific manner. Specifically, DNA methylation in non-CG context, namely CH methylation, has increased (hypermethylation) in neuronal gene bodies during human brain evolution, contributing to human-specific down-regulation of genes and co-expression modules. The effects of CH hypermethylation is particularly pronounced in early development and neuronal subtypes. In contrast, DNA methylation in CG context shows pronounced reduction (hypomethylation) in human brains, notably in cis-regulatory regions, leading to upregulation of downstream genes. We show that the majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and harbors strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage since the divergence from the chimpanzee lineage and carries significant genetic risk for schizophrenia. Therefore, recent epigenetic evolution of human cortex has shaped the cellular regulatory landscape and contributed to the increased vulnerability to neuropsychiatric diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Olig-2 Antibody Alexa Fluor 555 Conjugate, from rabbit, ALEXA FLUOR 555
Sigma-Aldrich
Anti-NeuN Antibody, clone A60, Alexa Fluor488 conjugated, clone A60, Chemicon®, from mouse