PT  - JOURNAL ARTICLE
AU  - Michael Song
AU  - Mark-Phillip Pebworth
AU  - Xiaoyu Yang
AU  - Armen Abnousi
AU  - Changxu Fan
AU  - Jia Wen
AU  - Jonathan D. Rosen
AU  - Mayank NK Choudhary
AU  - Xiekui Cui
AU  - Ian R. Jones
AU  - Seth Bergenholtz
AU  - Ugomma C. Eze
AU  - Ivan Juric
AU  - Bingkun Li
AU  - Lenka Maliskova
AU  - Weifang Liu
AU  - Alex A. Pollen
AU  - Yun Li
AU  - Ting Wang
AU  - Ming Hu
AU  - Arnold R. Kriegstein
AU  - Yin Shen
TI  - 3D Epigenomic Characterization Reveals Insights Into Gene Regulation and Lineage Specification During Corticogenesis
AID  - 10.1101/2020.02.24.963652
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.24.963652
4099  - http://biorxiv.org/content/early/2020/02/25/2020.02.24.963652.short
4100  - http://biorxiv.org/content/early/2020/02/25/2020.02.24.963652.full
AB  - Lineage-specific epigenomic changes during human corticogenesis have previously remained elusive due to challenges with tissue heterogeneity and sample availability. Here, we analyze cis-regulatory chromatin interactions, open chromatin regions, and transcriptomes for radial glia, intermediate progenitor cells, excitatory neurons, and interneurons isolated from mid-gestational human brain samples. We show that chromatin looping underlies transcriptional regulation for lineage-specific genes, with transcription factor motifs, families of transposable elements, and disease-associated variants enriched at distal interacting regions in a cell type-specific manner. A subset of promoters exhibit unusually high degrees of chromatin interactivity, which we term super interactive promoters. Super interactive promoters are enriched for critical lineage-specific genes, suggesting that interactions at these loci contribute to the fine-tuning of cell type-specific transcription. Finally, we present CRISPRview, a novel approach for validating distal interacting regions in primary cells. Our study presents the first characterization of cell type-specific 3D epigenomic landscapes during human corticogenesis, advancing our understanding of gene regulation and lineage specification during human brain development.