Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes
| العنوان: | Mapping cis-regulatory chromatin contacts in neural cells links neuropsychiatric disorder risk variants to target genes |
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| المؤلفون: | Michela Traglia, Si-Yao Lu, Li Gan, Kenneth Wu, Bingkun Li, Lenka Maliskova, Guo Li Ming, Bruce R. Conklin, Lauren A. Weiss, Fadi Jacob, Xiaoyu Yang, Kirsty Jamieson, Yin Shen, Michael Song, Tse Wai Tam, Chao Wang, Jesse R. Dixon, Jun Yao, Xingjie Ren, Luke M. Judge, Ian R. Jones, Yun Li, Hongjun Song |
| المصدر: | Nature genetics, vol 51, iss 8 Nature genetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Medical and Health Sciences, 0302 clinical medicine, 2.1 Biological and endogenous factors, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, Aetiology, Promoter Regions, Genetic, Induced pluripotent stem cell, Epigenomics, Neurons, Gene Editing, Regulation of gene expression, 0303 health sciences, Genome, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Mental Disorders, Chromosome Mapping, Single Nucleotide, Biological Sciences, Chromatin, Enhancer Elements, Genetic, Neurological, Functional genomics, Human, Biotechnology, Genetic Markers, Enhancer Elements, 1.1 Normal biological development and functioning, Induced Pluripotent Stem Cells, Computational biology, Biology, Polymorphism, Single Nucleotide, Article, Promoter Regions, 03 medical and health sciences, Genetic, Underpinning research, Genetics, Humans, Cell Lineage, Polymorphism, Enhancer, Gene, 030304 developmental biology, Stem Cell Research - Induced Pluripotent Stem Cell, Genome, Human, Human Genome, Neurosciences, Infant, Stem Cell Research, Brain Disorders, Gene Expression Regulation, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology |
| الوصف: | Mutations in gene regulatory elements have been associated with a wide range of complex neuropsychiatric disorders. However, due to their cell-type specificity and difficulties in characterizing their regulatory targets, the ability to identify causal genetic variants has remained limited. To address these constraints, we perform an integrative analysis of chromatin interactions, open chromatin regions and transcriptomes using promoter capture Hi-C, assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing, respectively, in four functionally distinct neural cell types: induced pluripotent stem cell (iPSC)-induced excitatory neurons and lower motor neurons, iPSC-derived hippocampal dentate gyrus-like neurons and primary astrocytes. We identify hundreds of thousands of long-range cis-interactions between promoters and distal promoter-interacting regions, enabling us to link regulatory elements to their target genes and reveal putative processes that are dysregulated in disease. Finally, we validate several promoter-interacting regions by using clustered regularly interspaced short palindromic repeats (CRISPR) techniques in human excitatory neurons, demonstrating that CDK5RAP3, STRAP and DRD2 are transcriptionally regulated by physically linked enhancers. |
| وصف الملف: | application/pdf |
| تدمد: | 1546-1718 1061-4036 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a735be77366982b363cc29770adc2b9 https://doi.org/10.1038/s41588-019-0472-1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3a735be77366982b363cc29770adc2b9 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15461718 10614036 |
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