PMID- 29307494 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20240213 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 172 IP - 1-2 DP - 2018 Jan 11 TI - The Dynamic Landscape of Open Chromatin during Human Cortical Neurogenesis. PG - 289-304.e18 LID - S0092-8674(17)31494-0 [pii] LID - 10.1016/j.cell.2017.12.014 [doi] AB - 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - de la Torre-Ubieta, Luis AU - de la Torre-Ubieta L AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Stein, Jason L AU - Stein JL AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. FAU - Won, Hyejung AU - Won H AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Opland, Carli K AU - Opland CK AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Liang, Dan AU - Liang D AD - Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA; UNC Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA. FAU - Lu, Daning AU - Lu D AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Geschwind, Daniel H AU - Geschwind DH AD - Neurogenetics Program, Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center for Autism Research and Treatment, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu. LA - eng GR - R01 MH094714/MH/NIMH NIH HHS/United States GR - R21 MH103877/MH/NIMH NIH HHS/United States GR - U01 MH103365/MH/NIMH NIH HHS/United States GR - R00 MH113823/MH/NIMH NIH HHS/United States GR - R01 MH110927/MH/NIMH NIH HHS/United States GR - U01 MH103392/MH/NIMH NIH HHS/United States GR - U19 HD035470/HD/NICHD NIH HHS/United States GR - U01 MH103346/MH/NIMH NIH HHS/United States GR - U01 MH103340/MH/NIMH NIH HHS/United States GR - R01 MH060233/MH/NIMH NIH HHS/United States GR - U01 MH103339/MH/NIMH NIH HHS/United States GR - K99 MH113823/MH/NIMH NIH HHS/United States GR - R21 MH105881/MH/NIMH NIH HHS/United States GR - P50 MH106934/MH/NIMH NIH HHS/United States GR - T32 GM067553/GM/NIGMS NIH HHS/United States GR - U54 HD087101/HD/NICHD NIH HHS/United States GR - R01 MH100027/MH/NIMH NIH HHS/United States GR - R01 MH105472/MH/NIMH NIH HHS/United States GR - P30 AI028697/AI/NIAID NIH HHS/United States GR - R00 MH102357/MH/NIMH NIH HHS/United States GR - R21 MH102791/MH/NIMH NIH HHS/United States GR - R01 MH105898/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180104 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Chromatin) RN - 0 (EOMES protein, human) RN - 0 (T-Box Domain Proteins) RN - EC 2.7.10.1 (FGFR2 protein, human) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2) SB - IM CIN - Cell. 2018 Jan 11;172(1-2):10-13. PMID: 29328907 CIN - Nat Rev Neurosci. 2018 Mar;19(3):120-121. PMID: 29386613 MH - Cell Line MH - Cells, Cultured MH - Cerebral Cortex/cytology/embryology/*metabolism MH - Chromatin/genetics/metabolism MH - *Chromatin Assembly and Disassembly MH - Enhancer Elements, Genetic MH - Female MH - *Gene Expression Regulation, Developmental MH - Humans MH - Male MH - *Neurogenesis MH - Neurons/cytology/*metabolism MH - Polymorphism, Genetic MH - Receptor, Fibroblast Growth Factor, Type 2/genetics/metabolism MH - T-Box Domain Proteins/genetics/metabolism PMC - PMC5924568 MID - NIHMS931857 OTO - NOTNLM OT - ATAC-seq OT - chromatin OT - enhancers OT - evolution OT - human neocortical development OT - transcription factors COIS- The authors declare no financial conflict of interest. EDAT- 2018/01/09 06:00 MHDA- 2019/01/01 06:00 PMCR- 2019/01/11 CRDT- 2018/01/09 06:00 PHST- 2017/03/14 00:00 [received] PHST- 2017/09/14 00:00 [revised] PHST- 2017/12/07 00:00 [accepted] PHST- 2018/01/09 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/01/09 06:00 [entrez] PHST- 2019/01/11 00:00 [pmc-release] AID - S0092-8674(17)31494-0 [pii] AID - 10.1016/j.cell.2017.12.014 [doi] PST - ppublish SO - Cell. 2018 Jan 11;172(1-2):289-304.e18. doi: 10.1016/j.cell.2017.12.014. Epub 2018 Jan 4.