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| Status |
Public on Jun 20, 2022 |
| Title |
Changes in gene expression in SMCHD1 knockout clones of HCT116 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Development of effective therapies for complex Mendelian disorders such as Facioscapulohumeral muscular dystrophy necessitates a clear understanding of the pathology of this disease. The inappropriate expression of DUX4-fl is believed to be responsible for the disease phenotype. We sought to understand the role of SMCHD1, an epigenetic modifier of the D4Z4 array, in DUX4-fl expression, by a TALEN mediated knockout of the gene in a model cell line HCT116. Analysis of SMCHD1 and DNMT knockouts of HCT116, along with patient cell lines highlighted the importance of epigenetic determinants of the disease and revealed a novel DUX4 isoform. We show that while SMCHD1 loss sensitizes cells to DUX4 expression by increasing transcription of unspliced product from D4Z4, splicing of the transcripts to generate disease associated DUX4-fl can only be induced by CpG hypomethylation and loss of heterochromatic histone marker H3K9me3. Additionally, telomere shortening has an effect similar to SMCHD1 loss, suggesting involvement of a telomere position effect in maintaining DUX4 repression. In light of our observations, we have developed a model for expression of DUX4-fl through a simultaneous loss of heterochromatin at D4Z4 and at the telomere, otherwise maintained by SMCHD1 that acts as a bridge between these two regions.
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| Overall design |
Samples include three replicate miroarray hybridizations of the parental cells (HCT116) and three replicates from three independent SMCHD1 knock-out clones (40, 41 and 43)
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| Contributor(s) |
Das S, Chadwick BP |
| Citation missing |
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| Submission date |
Jun 24, 2014 |
| Last update date |
Jun 20, 2022 |
| Contact name |
Sunny Das |
| E-mail(s) |
sdas@bio.fsu.edu
|
| Organization name |
Florida State University
|
| Department |
Biological Science
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| Lab |
Chadwick lab
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| Street address |
319 Stadium Drive
|
| City |
Tallahassee |
| State/province |
FL |
| ZIP/Postal code |
32306 |
| Country |
USA |
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| Platforms (1) |
| GPL16025 |
NimbleGen Homo sapiens Expression Array [100718_HG18_opt_expr] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA253508 |
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