Evolution of regulatory signatures in primate cortical neurons at cell-type resolution

Kozlenkov A, Vermunt MW, Apontes P, Li J, Hao K, Sherwood CC, Hof PR, Ely JJ, Wegner M, Mukamel EA, Creyghton MP, Koonin EV, Dracheva S (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 117

Pages Range: 28422-28432

Journal Issue: 45

DOI: 10.1073/pnas.2011884117

Abstract

The human cerebral cortex contains many cell types that likely underwent independent functional changes during evolution. However, cell-type–specific regulatory landscapes in the cortex remain largely unexplored. Here we report epigenomic and transcriptomic analyses of the two main cortical neuronal subtypes, glutamatergic projection neurons and GABAergic interneurons, in human, chimpanzee, and rhesus macaque. Using genome-wide profiling of the H3K27ac histone modification, we identify neuron-subtype–specific regulatory elements that previously went undetected in bulk brain tissue samples. Human-specific regulatory changes are uncovered in multiple genes, including those associated with language, autism spectrum disorder, and drug addiction. We observe preferential evolutionary divergence in neuron subtype-specific regulatory elements and show that a substantial fraction of pan-neuronal regulatory elements undergoes subtype-specific evolutionary changes. This study sheds light on the interplay between regulatory evolution and cell-type–dependent gene-expression programs, and provides a resource for further exploration of human brain evolution and function.

Authors with CRIS profile

Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

James J. Peters VA Medical Center US United States (USA) (US) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) University of California, San Diego US United States (USA) (US) Icahn School of Medicine at Mount Sinai US United States (USA) (US) George Washington University (GWU) US United States (USA) (US) Alamogordo Primate Facility (APF) US United States (USA) (US) US National Institutes of Health (NIH) US United States (USA) (US)

How to cite

APA:

Kozlenkov, A., Vermunt, M.W., Apontes, P., Li, J., Hao, K., Sherwood, C.C.,... Dracheva, S. (2020). Evolution of regulatory signatures in primate cortical neurons at cell-type resolution. Proceedings of the National Academy of Sciences of the United States of America, 117(45), 28422-28432. https://dx.doi.org/10.1073/pnas.2011884117

MLA:

Kozlenkov, Alexey, et al. "Evolution of regulatory signatures in primate cortical neurons at cell-type resolution." Proceedings of the National Academy of Sciences of the United States of America 117.45 (2020): 28422-28432.

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