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Cell-type and cytosine context-specific evolution of DNA methylation in the human brain

Authors :
Kazuya Toriumi
Stefano Berto
Devika Singh
Hyeonsoo Jeong
Thomas Layman
Iksoo Huh
Connor Douglas
Genevieve Konopka
Todd M. Preuss
Soojin V. Yi
Isabel Mendizabal
Paramita Chatterjee
Noriyoshi Usui
Publication Year :
2020
Publisher :
Cold Spring Harbor Laboratory, 2020.

Abstract

Cell-type specific epigenetic modifications are critical for brain development and neuropsychiatric diseases. Here we elucidate evolutionary origins of neuron- and oligodendrocyte-specific DNA methylation in human prefrontal cortex, and demonstrate dynamic and distinctive changes of CG and CH methylation. We show that the human brain has experienced pronounced reduction of CG methylation during evolution, which significantly contributed to cell-type specific active regulatory regions. On the other hand, a substantial increase of CH methylation occurred during human brain evolution, associated with fine-tuning expression in development and neuronal subtypes. The majority of differential CG methylation between neurons and oligodendrocytes originated before the divergence of hominoids and catarrhine monkeys, and carries strong signal for genetic risk for schizophrenia. Remarkably, a substantial portion of differential CG methylation between neurons and oligodendrocytes emerged in the human lineage and harbors additional genetic risk for schizophrenia, implicating epigenetic evolution of human cortex in increased vulnerability to neuropsychiatric diseases.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........884061deba567800db6ee8bc4b078379