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| Status |
Public on Feb 19, 2019 |
| Title |
Genome-Scale Transcriptional Regulatory Network Models of Psychiatric and Neurodegenerative Disorders |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Transcriptional regulatory changes in the developing and adult brain are prominent features of brain diseases, but the involvement of specific transcription factors (TFs) remains poorly understood. We integrated brain-specific DNase footprinting and TF-gene co-expression to reconstruct a transcriptional regulatory network (TRN) model for the human brain. We identified key regulator TFs whose predicted target genes were enriched for differentially expressed genes in the prefrontal cortex of individuals with psychiatric and neurodegenerative diseases. Many of these TFs were further implicated in the same diseases through disruption of their binding sites by disease-associated SNPs and associations of TF loci with disease risk. Using primary human neural stem cells, we validated network predictions that link the TF POU3F2 to schizophrenia and bipolar disorder via both cis- and trans-acting mechanisms. Our models of brain-specific TF binding sites and target genes provide a resource for network analysis of brain diseases.
GPL 17077 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381
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| Overall design |
A transcription factor related to psychiatric disease, POU3F2, is overexpressed in primary human neural stem cells. RNA expression at 3 and 10 days post-puromycin selection is analyzed using microarrays as compared to cells transduced with a control vector that does not contain the POU3F2 cassette.
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| Web link |
https://www.ncbi.nlm.nih.gov/pubmed/30772379
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| |
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| Contributor(s) |
Pearl JR, Ament SA |
| Citation(s) |
30772379 |
| |
| Submission date |
Aug 01, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jocelynn Renee Pearl |
| E-mail(s) |
jpearl@uw.edu
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| Phone |
2067322166
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| Organization name |
Institute for Systems Biology
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| Street address |
401 Terry Ave N
|
| City |
Seattle |
| State/province |
Washington |
| ZIP/Postal code |
98109 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA396735 |
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