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Status |
Public on Sep 11, 2012 |
Title |
Splicing switch of an epigenetic regulator by RNA helicases promotes tumor-cell invasiveness |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Both epigenetic and splicing regulation contribute to tumor progression, but the potential links between these two levels of gene-expression regulation in pathogenesis are not well understood. Here, we report that the mouse and human RNA helicases ddx17 and ddx5 contribute to tumor-cell invasiveness by regulating alternative splicing of several DNA- and chromatin-binding factors, including the macroH2A1 histone. We show that macroH2A1 splicing isoforms differentially regulate the transcription of a set of genes involved in redox metabolism. In particular, the SOD3 gene that encodes the extracellular superoxide dismutase and plays a part in cell migration is regulated in an inverse manner by macroH2A1 splicing isoforms. These findings reveal a new regulatory pathway in which splicing factors control the expression of histone-variant isoforms that in turn drive a transcription program to switch tumor cells to an invasive phenotype.
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Overall design |
We analyzed 4T1 cells depleted or not for ddx5 and ddx17 RNA helicases using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. Four techinical replicates were performed. We analyzed 4T1 cells depleted for ddx5 and ddx17 RNA helicases and macroH2A1.1 or macroH2A1.2 using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. Three techinical replicates were performed.
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Contributor(s) |
Dardenne E, Pierredon S, Driouch K, Gratadou L, Lacroix-Triki M, Espinoza MP, Zonta E, Germann S, Mortada H, Villemin J, Dutertre M, Lidereau R, Vagner S, Auboeuf D |
Citation(s) |
23022728 |
Submission date |
Sep 10, 2012 |
Last update date |
Mar 06, 2018 |
Contact name |
Etienne Dardenne |
E-mail(s) |
etienne.dardenne@gmail.com
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Organization name |
Weill Cornell Medecine
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Department |
Pathology
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Lab |
Rickman
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Street address |
1300 York Avenue
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10021 |
Country |
USA |
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Platforms (1) |
GPL6096 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version] |
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Samples (14)
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Relations |
BioProject |
PRJNA174786 |