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| Status |
Public on Apr 12, 2017 |
| Title |
Bi-directional regulation between circadian rhythm and neurodegeneration-associated FUS |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Circadian rhythms are daily physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have long been associated with various neurodegenerative diseases. Abnormal sleep-wake cycle often precedes the onset of cognitive and motor symptoms in patients, while the pathological changes may further exacerbate the disturbance in circadian cycle. It is unclear whether dysregulated circadian rhythm is a consequence of, or a contributing factor for, neurodegeneration. In addition, the evidence directly connecting the neurodegeneration-associated proteins to core circadian clock gene expression remains sparse. Here we show that FUS, a RNA-binding protein implicated in the pathogenesis of ALS and frontotemporal dementia, exhibits a bi-directional regulation with circadian rhythm. Our meta-analysis of RNAseq datasets and subsequent biochemical analysis revealed FUS as a gene regulated by circadian oscillation. Furthermore, NR1D1 binds the FUS promoter and regulates the amplitude of FUS oscillation. Meanwhile, FUS is recruited by transcriptional co-repressor PSF, and is found in the same complex as Bmal-Clock to repress Per2 expression. More strikingly, in cells and brain tissues from homozygous knock-in rats, the pathogenic R521C mutant FUS significantly alters the oscillation patterns of core circadian genes even at young age. Therefore, our results have revealed a novel bi-directional mechanism whereby dysregulated circadian clock and FUS expression may exacerbate neurodegeneration via mutual influence.
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| Overall design |
Cortex, liver, spinal cord profiles of 3.3-month old WT and R521C knock in rat were collected at CT0, CT4, CT8, CT12, CT16, CT20 and generated by deep sequencing using Illumina HiSeq 2000.
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| Contributor(s) |
Jiang X, Wang H, Zhang T, Yan J, Xu J |
| Citation(s) |
28335007 |
| Submission date |
Feb 04, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Haifang Wang |
| E-mail(s) |
wanghf810501@gmail.com
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| Organization name |
PICB
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| Department |
functional genomics group
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| Street address |
NO 320, Yueyang Road
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| City |
ShangHai |
| ZIP/Postal code |
200031 |
| Country |
China |
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| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
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| Samples (35)
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| Relations |
| BioProject |
PRJNA310841 |
| SRA |
SRP069297 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE77572_RAW.tar |
5.1 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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