Journal
CELL
Volume 184, Issue 3, Pages 723-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.01.001
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Funding
- Strategic Priority Research Program [XDB13010000]
- National Natural Science Foundation of China [U2002207, 31730088, 31621062, 91631306, 32000406, 31871266, 71532001, 11661141019, 2019YFA0709501, 61621003]
- National Key Research and Development Program of China [2016YFA0100103]
- National Ten Thousand Talent Program for Young Top-notch Talents
- Ten Thousand Talents Project of Yunnan Province of China
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The study reveals human-specific chromatin structure changes in the brain, which play crucial roles in neural circuit formation and plasticity.
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 generate 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.
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