Title
Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia
UMMS Affiliation
Department of Psychiatry; Program in Bioinformatics and Integrative Biology
Publication Date
2019-10-17
Document Type
Article
Disciplines
Amino Acids, Peptides, and Proteins | Genetic Phenomena | Genomics | Nervous System | Neuroscience and Neurobiology | Nucleic Acids, Nucleotides, and Nucleosides | Psychiatry | Psychiatry and Psychology | Translational Medical Research
Abstract
Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia. Here, we performed analysis of open chromatin landscape of gene promoters in prefrontal cortical (PFC) neurons from schizophrenic patients. We cataloged cell-type-based epigenetic signals of transcriptional start sites (TSS) marked by histone H3-K4 trimethylation (H3K4me3) across the genome in PFC from multiple schizophrenia subjects and age-matched control individuals. One of the top-ranked chromatin alterations was found in the major histocompatibility (MHC) locus on chromosome 6 highlighting the overlap between genetic and epigenetic risk factors in schizophrenia. The chromosome conformation capture (3C) analysis in human brain cells revealed the architecture of multipoint chromatin interactions between the schizophrenia-associated genetic and epigenetic polymorphic sites and distantly located HLA-DRB5 and BTNL2 genes. In addition, schizophrenia-specific chromatin modifications in neurons were particularly prominent for non-coding RNA genes, including an uncharacterized LINC01115 gene and recently identified BNRNA_052780. Notably, protein-coding genes with altered epigenetic state in schizophrenia are enriched for oxidative stress and cell motility pathways. Our results imply the rare individual epigenetic alterations in brain neurons are involved in the pathogenesis of schizophrenia.
Keywords
Epigenetics in the nervous system, Schizophrenia
Rights and Permissions
© The Author(s) 2019. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any mediumor format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41398-019-0596-1
Source
Transl Psychiatry. 2019 Oct 17;9(1):256. doi: 10.1038/s41398-019-0596-1. Link to article on publisher's site
Journal/Book/Conference Title
Translational psychiatry
Related Resources
PubMed ID
31624234
Repository Citation
Gusev FE, Reshetov DA, Mitchell AC, Andreeva TV, Dincer A, Grigorenko AP, Fedonin G, Halene T, Aliseychik M, Filippova E, Weng Z, Akbarian S, Rogaev EI. (2019). Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia. Open Access Articles. https://doi.org/10.1038/s41398-019-0596-1. Retrieved from https://escholarship.umassmed.edu/oapubs/4033
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Genetic Phenomena Commons, Genomics Commons, Nervous System Commons, Neuroscience and Neurobiology Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Psychiatry Commons, Psychiatry and Psychology Commons, Translational Medical Research Commons