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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Sdoi
10.1073/pnas.2011884117subject
Has Abstractpub_date
2020-11-10 00:00:00pages
28422-28432issue
45eissn
0027-8424issn
1091-6490pii
2011884117journal_volume
117pub_type
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