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bioRxiv · 10.1101/2024.07.24.605026

Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis

Li, C.·Zhu, L.·Su, B.·Jia, L.·Hou, Y.·Cui, Z.·Luo, X.·Duan, J.·Guo, J.·Shi, M.·Chen, H.·Li, T.·Zhang, F.
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Abstract

The chromatin in the human brain cortex shows more enhancer-enhancer contacts than in macaques and mice, yet the organization of these contacts across cellular states and their mechanisms remain unclear. Here, we developed SCOPE-C, a cost-effective technique designed for mapping DNase I Hypersensitive Sites and their spatial interactions, with the potential for scalability to single-cell resolution. Employing SCOPE-C, we generated a comprehensive chromatin map detailing cis-regulatory elements in four cell types during neurogenesis in human, macaque, and mouse fetal cortex. This map introduces a model of long-range enhancer networks that regulate gene transcription during human cortical neurogenesis. In this model, CTCF-mediated loop extrusion forms stripes of enhancer interaction hubs extending up to 10 Mb in human Excitatory Neurons. Enriched with human-specific enhancers and neuropsychiatric disorder-linked SNPs, these remarkably long-range networks predominantly control EN marker genes, suggesting their critical role in robust gene expression during human cortical neurogenesis.

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Li, C., Zhu, L., Su, B., Jia, L., Hou, Y., Cui, Z., Luo, X., Duan, J., Guo, J., Shi, M., Chen, H., Li, T., Zhang, F.. 2024-07-25. Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis. https://doi.org/10.1101/2024.07.24.605026

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