生物
基因
精神分裂症(面向对象编程)
转录因子
人脑
计算生物学
脚印
转录调控
疾病
基因调控网络
神经科学
调节器
遗传学
调节顺序
基因表达调控
前额叶皮质
基因表达
医学
精神科
认知
病理
作者
Jocelynn Pearl,Carlo Colantuoni,Dani E Bergey,Cory C. Funk,Paul Shannon,B. Basu,Alex M. Casella,Rediet T. Oshone,Leroy Hood,Nathan D. Price,Seth A. Ament
出处
期刊:Cell systems
[Elsevier]
日期:2019-02-01
卷期号:8 (2): 122-135.e7
被引量:48
标识
DOI:10.1016/j.cels.2019.01.002
摘要
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.
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