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

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

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

doi

10.1073/pnas.2011884117

subject

Has Abstract

pub_date

2020-11-10 00:00:00

pages

28422-28432

issue

45

eissn

0027-8424

issn

1091-6490

pii

2011884117

journal_volume

117

pub_type

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