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Evolutionary changes in promoter and enhancer activity during human corticogenesis

Science  06 Mar 2015:
Vol. 347, Issue 6226, pp. 1155-1159
DOI: 10.1126/science.1260943

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Of mice, men, and macaque brains

The human brain represents a unique evolutionary trajectory. To better understand how the human brain came to be, Reilly et al. sought to identify changes in gene expression between mice, macaques, and humans. They compared epigenetic marks in the embryonic cortex, which revealed changes in gene regulation in biological pathways associated with cortical development.

Science, this issue p. 1155

Abstract

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.

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