Cell Type and Species-specific Patterns in Neuronal and Non-neuronal Methylomes of Human and Chimpanzee Cortices
Autor: | Nady El Hajj, Thomas Haaf, Carsten P Ade, Julia Böck, Eberhard Schneider, Ronald E. Bontrop, Armin Giese, Ivanela Kondova, Marcus Dittrich, Christian W. Remmele, Tobias Müller, Stephan P. Persengiev, Theo F. J. Kraus |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cell type Lineage (genetic) Pan troglodytes Cognitive Neuroscience Biology cortex methylome human–chimpanzee epigenetic divergence Evolution Molecular 03 medical and health sciences Cellular and Molecular Neuroscience Species Specificity medicine Animals Humans Epigenetics Aged Cerebral Cortex Neurons Genetics human brain evolution RRBS Mental Disorders Original Articles Human brain Methylation DNA Methylation neuronal vs. non-neuronal cells 030104 developmental biology Histone medicine.anatomical_structure Differentially methylated regions nervous system Reduced representation bisulfite sequencing Metabolome biology.protein Female Neuroglia Genome-Wide Association Study |
Zdroj: | Cerebral Cortex (New York, NY) |
ISSN: | 1460-2199 1047-3211 |
Popis: | 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. |
Databáze: | OpenAIRE |
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