3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis

Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may lead to the formation of new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution. Overall design: Hi-C, RNA-seq, ChIP-seq and DNase-seq in macaque cortical development NOTE: The GSM4974109-GSM4974114 processed data .hic files were replaced and the CP_cis_allValidPairs.hic, GZ_cis_allValidPairs.hic were added on Oct 25, 2022 as the previous files were incomplete. The GSM4974109-GSM4974114 raw data have been updated with additional/technical replicate runs on Feb 20, 2023.