Cell type and species-specific patterns in neuronal and non-neuronal methylomes of human and chimpanzee cortices

Julia Böck, Christian W. Remmele, Marcus Dittrich, Tobias Müller, Ivanela Kondova, Stephan Persengiev, Ronald E. Bontrop, Carsten P. Ade, Theo F.J. Kraus, Armin Giese, Nady El Hajj, Eberhard Schneider, Thomas Haaf*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Epigenetic changes have likely contributed to the large size and enhanced cognitive abilities of the human brain which evolved within the last 2 million years after the human-chimpanzee split. Using reduced representation bisulfite sequencing, we have compared the methylomes of neuronal and non-neuronal cells from 3 human and 3 chimpanzee cortices. Differentially methylated regions (DMRs) with genome-wide significance were enriched in specific genomic regions. Intraspecific methylation differences between neuronal and non-neuronal cells were approximately 3 times more abundant than interspecific methylation differences between human and chimpanzee cell types. The vast majority (>90%) of human intraspecific DMRs (including DMRs in retrotransposons) were hypomethylated in neurons, compared with glia. Intraspecific DMRs were enriched in genes associated with different neuropsychiatric disorders. Interspecific DMRs were enriched in genes showing human-specific brain histone modifications. Human-chimpanzee methylation differences were much more frequent in non-neuronal cells (n. DMRs = 666) than in neurons (n. DMRs = 96). More than 95% of interspecific DMRs in glia were hypermethylated in humans. Although without an outgroup we cannot assign whether a change in methylation occurred in the human or chimpanzee lineage, our results are consistent with a wave of methylation affecting several hundred non-neuronal genes during human brain evolution.

Original languageEnglish
Pages (from-to)3724-3739
Number of pages16
JournalCerebral Cortex
Volume28
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Keywords

  • RRBS
  • cortex methylome
  • human brain evolution
  • human-chimpanzee epigenetic divergence
  • neuronal vs. non-neuronal cells

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