Evolutionary changes in promoter and enhancer activity during corticogenesis (non-human)

Evolutionary changes in gene regulation during cortical development likely contributed to the expansion and specialization of the cortex. However, the lack of a regulatory map of the embryonic cortex has hindered identification of these changes and the biological processes they influenced. We performed genome-wide epigenetic profiling to compare promoter and enhancer activity during corticogenesis in rhesus and mouse. We identified 2,855 promoters and 8,996 enhancers that have gained activity in based on increased epigenetic marking. To detect biological pathways enriched for these changes, we mapped promoters and enhancers exhibiting epigenetic gains onto modules of co-expressed genes constructed using spatio-temporally rich expression data from developing cortex. We identified multiple modules enriched in lineage epigenetic gains. Gains in enriched modules were associated with genes functioning in neuronal proliferation and migration, cortical patterning, and the extracellular matrix. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes in corticogenesis, providing insight into cortical evolution. For mouse samples, two biological replicates each from four cortical tissues (embryonic day 11.5 (E11.5), E14.5, E17.5 frontal, and E17.5 occipital. For Rhesus, two biological replicates each from 12 p.c.w. frontal and 12 p.c.w. occipital and one replicate from 8 p.c.w. Each replicate is comprised of H3K27ac and H3K4me2 ChIPs in addition to a shared input control.