Comparison of chromatin accessibility landscapes during early development of prefrontal cortex between rhesus macaque and human

Epigenetic information regulates gene expression and development. However, our understanding of the evolution of epigenetic regulation on brain development in primates is limited. Here, we compared chromatin accessibility landscapes and transcriptomes during fetal prefrontal cortex (PFC) development between rhesus macaques and humans. A total of 304,761 divergent DNase I-hypersensitive sites (DHSs) are identified between rhesus macaques and humans, although many of these sites share conserved DNA sequences. Interestingly, most of the cis -elements linked to orthologous genes with dynamic expression are divergent DHSs. Orthologous genes expressed at earlier stages tend to have conserved cis -elements, whereas orthologous genes specifically expressed at later stages seldom have conserved cis -elements. These genes are enriched in synapse organization, learning and memory. Notably, DHSs in the PFC at early stages are linked to human educational attainment and cognitive performance. Collectively, the comparison of the chromatin epigenetic landscape between rhesus macaques and humans suggests a potential role for regulatory elements in the evolution of differences in cognitive ability between non-human primates and humans.