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| Status |
Public on Jul 03, 2014 |
| Title |
DUX4-induced gene expression is the major molecular signature in FSHD skeletal muscle |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Facioscapulohumeral dystrophy (FSHD) is caused by decreased epigenetic repression of the D4Z4 macrosatellite array and recent studies have shown that this results in the expression of low levels of the DUX4 mRNA in skeletal muscle. Several other mechanisms have been suggested for FSHD pathophysiology and it remains unknown whether DUX4 expression can account for most of the molecular changes seen in FSHD. Since DUX4 is a transcription factor, we used RNA-seq to measure gene expression in muscle cells transduced with DUX4, and in muscle cells and biopsies from control and FSHD individuals. We show that DUX4 target gene expression is the major molecular signature in FSHD muscle together with a gene expression signature consistent with an immune cell infiltration. In addition, one unaffected individual without a known FSHD-causing mutation showed expression of DUX4 target genes. This individual has a sibling with FSHD and also without a known FSHD-causing mutation, suggesting the presence of yet unidentified modifier locus for DUX4 expression and FSHD. These findings demonstrate that expression of DUX4 accounts for the majority of the gene expression changes in FSHD skeletal muscle together with an immune cell infiltration.
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| |
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| Overall design |
RNA-seq for muscle cells and biopsies from control and FSHD individuals.
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| |
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| Contributor(s) |
Yao Z, Snider L, Balog J, Lemmers RF, van der Maarel SM, Tawil R, Tapscott SJ |
| Citation(s) |
24861551, 25789155 |
| |
| Submission date |
Apr 14, 2014 |
| Last update date |
Jun 13, 2019 |
| Contact name |
Stephen Tapscott |
| E-mail(s) |
stapscot@fredhutch.org
|
| Organization name |
Fred Hutch Cancer Research Center
|
| Department |
Human Biology
|
| Lab |
Tapscott
|
| Street address |
1100 Fairview N. Ave
|
| City |
Seattle |
| State/province |
WASHINGTON |
| ZIP/Postal code |
98103 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (38)
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|
| Relations |
| BioProject |
PRJNA244584 |
| SRA |
SRP043221 |
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