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Core transcriptional regulatory circuits in prion diseases

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Authors
Kim, Taek-Kyun; Lee, Inyoul; Cho, Ji-Hoon; Canine, Brenda; Keller, Andrew; Price, Nathan D; Hwang, Daehee; Carlson, George; Hood, Leroy
Issue Date
2020-01-20
Publisher
BMC
Citation
Molecular Brain, 13(1):10
Keywords
Murine PrP-prion diseaseGene expressionTranscriptional regulatory circuitsFeed-forward loopsBrain cell type
Abstract
Complex diseases involve dynamic perturbations of pathophysiological processes during disease progression. Transcriptional programs underlying such perturbations are unknown in many diseases. Here, we present core transcriptional regulatory circuits underlying early and late perturbations in prion disease. We first identified cellular processes perturbed early and late using time-course gene expression data from three prion-infected mouse strains. We then built a transcriptional regulatory network (TRN) describing regulation of early and late processes. We found over-represented feed-forward loops (FFLs) comprising transcription factor (TF) pairs and target genes in the TRN. Using gene expression data of brain cell types, we further selected active FFLs where TF pairs and target genes were expressed in the same cell type and showed correlated temporal expression changes in the brain. We finally determined core transcriptional regulatory circuits by combining these active FFLs. These circuits provide insights into transcriptional programs for early and late pathophysiological processes in prion disease.
ISSN
1756-6606
Language
English
URI
https://doi.org/10.1186/s13041-020-0551-3

http://hdl.handle.net/10371/164927
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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