Evolutionary genomics. Evolutionary changes in promoter and enhancer activity during human corticogenesis.
Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Steven K
SK
Reilly
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Jun
J
Yin
Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
Albert E
AE
Ayoub
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Deena
D
Emera
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA.
Jing
J
Leng
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Justin
J
Cotney
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Richard
R
Sarro
Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
Pasko
P
Rakic
Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.
James P
JP
Noonan
D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008253:Macaca mulatta; D051379:Mice; D038081:Organogenesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats