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Chunk #27 — Regulatory networks

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Comprehensive functional genomic resource and integrative model for the human brain.
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Collectively, we generated a full regulatory network, linking enhancers, TFs, and target genes (fig. S42). This includes 43,181 proximal and 42,681 distal linkages involving 11,573 protein-encoding target genes (TF–to–target gene via promoter for proximal versus via enhancer–target gene connection for distal) (Fig. 5A) (15, 21). As functioning regulatory connections reflect cell type, we also generated potential cell-type–specific regulatory networks (Fig. 5, F and G, and fig. S44). In these, we found a number of well-known TFs associated with brain development—e.g., NEUROG1, DLGAP2, and MEF2A for excitatory neurons and GAD1, GAD2, and LHX6 for inhibitory neurons (Fig. 5G) (43–46). Lastly, for broad utility on the resource website, we also provide an expanded regulatory network with slightly different parameterization (fig. S42).