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Nat Neurosci. 2016 Mar;19(3):494-503. doi: 10.1038/nn.4229. Epub 2016 Jan 25.

Epigenomic annotation of gene regulatory alterations during evolution of the primate brain.

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Hubrecht Institute-KNAW and University Medical Center Utrecht, Utrecht, the Netherlands.
Biomedical Primate Research Center, Rijswijk, the Netherlands.


Although genome sequencing has identified numerous noncoding alterations between primate species, which of those are regulatory and potentially relevant to the evolution of the human brain is unclear. Here we annotated cis-regulatory elements (CREs) in the human, rhesus macaque and chimpanzee genomes using chromatin immunoprecipitation followed by sequencing (ChIP-seq) in different anatomical regions of the adult brain. We found high similarity in the genomic positioning of rhesus macaque and human CREs, suggesting that the majority of these elements were already present in a common ancestor 25 million years ago. Most of the observed regulatory changes between humans and rhesus macaques occurred before the ancestral separation of humans and chimpanzees, leaving a modest set of regulatory elements with predicted human specificity. Our data refine previous predictions and hypotheses on the consequences of genomic changes between primate species and allow the identification of regulatory alterations relevant to the evolution of the brain.

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