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Common Schizophrenia Risk Variants Are Enriched in Open Chromatin Regions of Human Glutamatergic Neurons by Hauberg, Mads E.; Creus-Muncunill, Jordi; Bendl, Jaroslav; Kozlenkov, Alexey; Zeng, Biao; Corwin, Chuhyon; Chowdhury, Sarah; Kranz, Harald; Hurd, Yasmin L.; Wegner, Michael; BÃ ̧rglum, Anders D.; Dracheva, Stella; Ehrlich, Michelle E.; Fullard, John F.; Roussos, Panos is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
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## Abstract The chromatin landscape of human brain cells encompasses key information to understanding brain function. Here we use ATAC-seq to profile the chromatin structure in four distinct populations of cells (glutamatergic neurons, GABAergic neurons, oligodendrocytes, and microglia/astrocytes) from three different brain regions (anterior cingulate cortex, dorsolateral prefrontal cortex, and primary visual cortex) in human postmortem brain samples. We find that chromatin accessibility varies greatly by cell type and, more moderately, by brain region, with glutamatergic neurons showing the largest regional variability. Transcription factor footprinting implicates cell-specific transcriptional regulators and infers cell-specific regulation of protein-coding genes, long intergenic noncoding RNAs and microRNAs. In vivo transgenic mouse experiments validate the cell type specificity of several of these human-derived regulatory sequences. We find that open chromatin regions in glutamatergic neurons are enriched for neuropsychiatric risk variants, particularly those associated with schizophrenia. Integration of cell-specific chromatin data with a bulk tissue study of schizophrenia brai
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- Author
- Hauberg, Mads E.; Creus-Muncunill, Jordi; Bendl, Jaroslav; Kozlenkov, Alexey; Zeng, Biao; Corwin, Chuhyon; Chowdhury, Sarah; Kranz, Harald; Hurd, Yasmin L.; Wegner, Michael; BÃ ̧rglum, Anders D.; Dracheva, Stella; Ehrlich, Michelle E.; Fullard, John F.; Roussos, Panos
- Publisher
- Nature Publishing Group; Springer Science and Business Media LLC; [London]: Nature Publishing Group, 2010-; Society for Mining, Metallurgy and Exploration Inc.; Research Square (ISSN 2041-1723)
- Published
- 2020
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)