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

View ORCID ProfileHyeonsoo 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
doi: https://doi.org/10.1101/2020.07.14.203034
Hyeonsoo Jeong
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
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  • ORCID record for Hyeonsoo Jeong
Isabel Mendizabal
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
2Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 801A, Derio, 48160, Spain
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Stefano Berto
3Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA
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Paramita Chatterjee
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Thomas Layman
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Noriyoshi Usui
3Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA
4Center for Medical Research and Education and Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan
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Kazuya Toriumi
3Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA
5Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, 156-8506, Japan
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Connor Douglas
3Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA
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Devika Singh
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
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Iksoo Huh
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
6College of Nursing and The Research Institute of Nursing Science, Seoul National University, Seoul, 03080, South Korea
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Todd M. Preuss
7Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, and Department of Pathology, Emory University School of Medicine, Atlanta, GA 30329, USA
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Genevieve Konopka
3Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA
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  • For correspondence: Genevieve.Konopka@utsouthwestern.edu soojinyi@gatech.edu
Soojin V. Yi
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
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  • For correspondence: Genevieve.Konopka@utsouthwestern.edu soojinyi@gatech.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • updated the acknowledgement section.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 16, 2020.
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Cell-type and cytosine context-specific evolution of DNA methylation in the human brain
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
bioRxiv 2020.07.14.203034; doi: https://doi.org/10.1101/2020.07.14.203034
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Cell-type and cytosine context-specific evolution of DNA methylation in the human brain
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
bioRxiv 2020.07.14.203034; doi: https://doi.org/10.1101/2020.07.14.203034

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