The Dynamic Landscape of Open Chromatin during Human Cortical Neurogenesis
Open accessAbstract
Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. We link distal regulatory elements (DREs) to their cognate gene(s) together with chromatin interaction data and show that target genes of human-gained enhancers (HGEs) regulate cortical neurogenesis and are enriched in outer radial glia, a cell type linked to human cortical evolution. We experimentally validate the regulatory effects of predicted enhancers for FGFR2 and EOMES. We observe that common genetic variants associated with educational attainment, risk for neuropsychiatric disease, and intracranial volume are enriched within regulatory elements involved in cortical neurogenesis, demonstrating the importance of this early developmental process for adult human cognitive function.
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The major pathogenic mechanism of copy number variants is presumed to be dosage sensitivity of genes within the variant, although distal regulatory effects on genes outside the variant are also plausible.
“the major pathogenic mechanism is presumed to be dosage-sensitivity of genes in the CNV although distal regulatory effects on genes outside of the CNV are also plausible (de la Torre-Ubieta et al., 2018)”
From Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders (2019) · cites this paper as de la Torre-Ubieta et al., 2018
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Self-citation
- Authors
- de la Torre-Ubieta, L., Stein, J. L., Won, H., Opland, C. K., Liang, D., Lu, D., & Geschwind, D. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of California, Los Angeles (US)
- Corresponding author
- Geschwind, Daniel H.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 172
- Issue
- 1-2
- Pages
- 289-304.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5924568
- OpenAlex
- W2782160930
- Cited by
- 353
- References
- 90
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 32 · 2023: 54 · 2022: 41 · 2021: 45 · 2020: 66 · 2019: 44 · 2018: 27
- FWCI
- 16.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- NIH (5R37MH060233, 5R01MH100027, 3U01MH103339, 1R01MH110927, 1R01MH094714, R00MH102357, K99MH113823)
- California Institute for Regenerative Medicine (CIRM)-BSCRC Training Grant (TG2-01169)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- open chromatin, cortical neurogenesis, non-coding regulatory elements, distal regulatory elements, chromatin accessibility, enhancer-gene interactions, outer radial glia, cortical development, FGFR2, Eomes, educational attainment, intracranial volume, human brain evolution
- MeSH terms
- Cell Line, Cells, Cultured, Cerebral Cortex, Chromatin, Enhancer Elements, Genetic, Female, Humans, Male, Neurons, Polymorphism, Genetic, Gene Expression Regulation, Developmental, T-Box Domain Proteins, Chromatin Assembly and Disassembly, Receptor, Fibroblast Growth Factor, Type 2, Neurogenesis
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