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Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis
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Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis
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Paper
Long-Range Enhancer Networks Gradually Emerge as Key Regulators During Human Cortical Neurogenesis
2024
Overview
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.
Publisher
Cold Spring Harbor Laboratory
Subject
