Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia
| Autor: | Tobias B. Halene, Denis A. Reshetov, Gennady G. Fedonin, Schahram Akbarian, Zhiping Weng, Tatiana Andreeva, Evgeny I. Rogaev, Elena Filippova, Amanda C. Mitchell, Fedor Gusev, Anastasia P. Grigorenko, Aslihan Dincer, Maria Aliseychik |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Prefrontal Cortex Locus (genetics) Article lcsh:RC321-571 Epigenesis Genetic Chromosome conformation capture Histones 03 medical and health sciences Cellular and Molecular Neuroscience Young Adult 0302 clinical medicine Humans Epigenetics Epigenetics in the nervous system lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Gene Biological Psychiatry 030304 developmental biology Genetics Neurons 0303 health sciences biology Butyrophilins DNA Methylation Middle Aged Chromatin 3. Good health HLA-DRB5 Chains Psychiatry and Mental health Histone DNA methylation biology.protein Schizophrenia H3K4me3 RNA Long Noncoding Transcription Initiation Site 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry Translational Psychiatry, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2158-3188 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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