Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA315286 | ENA |
REPOSITORIES: ENA
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Project description:Background: The bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development and susceptibility to schizophrenia and bipolar disorder. Results: To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L, by a series of investigations and integration of functional molecular data with human genetic data. We present several novel protein interactions of BRD1, including proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large data sets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk. Conclusion: Our results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g.striatum, hippocampus, and amygdala at mid fetal stages. 9 expression arrays performed in HEK293T cells
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