Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

Bas Castelijns; Mirna L Baak; Ilia S Timpanaro; Caroline R M Wiggers; Marit W Vermunt; Peng Shang; Ivanela Kondova; Geert Geeven; Valerio Bianchi; Wouter de Laat; Niels Geijsen; Menno P Creyghton

doi:10.1038/s41467-019-14269-w

Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

Bas Castelijns, Mirna L Baak, Ilia S Timpanaro, Caroline R M Wiggers, Marit W Vermunt, Peng Shang, Ivanela Kondova, Geert Geeven, Valerio Bianchi, Wouter de Laat, Niels Geijsen, Menno P Creyghton

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

28 Citaten (Scopus)

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Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

Originele taal-2	Engels
Pagina's (van-tot)	301
Tijdschrift	Nature Communications
Volume	11
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-019-14269-w
Status	Gepubliceerd - 16 jan. 2020

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Castelijns, B., Baak, M. L., Timpanaro, I. S., Wiggers, C. R. M., Vermunt, M. W., Shang, P., Kondova, I., Geeven, G., Bianchi, V., de Laat, W., Geijsen, N., & Creyghton, M. P. (2020). Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients. Nature Communications, 11(1), 301. https://doi.org/10.1038/s41467-019-14269-w

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abstract = "Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.",

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AU - Shang, Peng

AU - Kondova, Ivanela

AU - Geeven, Geert

AU - Bianchi, Valerio

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AU - Geijsen, Niels

AU - Creyghton, Menno P

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AB - Speciation is associated with substantial rewiring of the regulatory circuitry underlying the expression of genes. Determining which changes are relevant and underlie the emergence of the human brain or its unique susceptibility to neural disease has been challenging. Here we annotate changes to gene regulatory elements (GREs) at cell type resolution in the brains of multiple primate species spanning most of primate evolution. We identify a unique set of regulatory elements that emerged in hominins prior to the separation of humans and chimpanzees. We demonstrate that these hominin gains perferentially affect oligodendrocyte function postnatally and are preferentially affected in the brains of autism patients. This preference is also observed for human-specific GREs suggesting this system is under continued selective pressure. Our data provide a roadmap of regulatory rewiring across primate evolution providing insight into the genomic changes that underlie the emergence of the brain and its susceptibility to neural disease.

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KW - Chromatin Immunoprecipitation

KW - Chromosomes/chemistry

KW - Disease Susceptibility

KW - Evolution, Molecular

KW - Female

KW - Gene Expression Regulation

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KW - Hominidae/genetics

KW - Humans

KW - Macaca mulatta

KW - Oligodendroglia/metabolism

KW - Pan troglodytes

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Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients

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